Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)
Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.
A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.
An enzyme that catalyzes the transfer of a methyl group from S-ADENOSYLMETHIONINE to the 5-position of CYTOSINE residues in DNA.
Inorganic salts of sulfurous acid.
A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
A pyrimidine base that is a fundamental unit of nucleic acids.
The systematic study of the global gene expression changes due to EPIGENETIC PROCESSES and not due to DNA base sequence changes.
Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.
A methylated nucleotide base found in eukaryotic DNA. In ANIMALS, the DNA METHYLATION of CYTOSINE to form 5-methylcytosine is found primarily in the palindromic sequence CpG. In PLANTS, the methylated sequence is CpNpGp, where N can be any base.
The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992)
Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.
Highly repeated sequences, 6K-8K base pairs in length, which contain RNA polymerase II promoters. They also have an open reading frame that is related to the reverse transcriptase of retroviruses but they do not contain LTRs (long terminal repeats). Copies of the LINE 1 (L1) family form about 15% of the human genome. The jockey elements of Drosophila are LINEs.
Methylases that are specific for CYTOSINE residues found on DNA.
A subclass of enzymes of the transferase class that catalyze the transfer of a methyl group from one compound to another. (Dorland, 28th ed) EC 2.1.1.
An enzyme that catalyzes the methylation of the epsilon-amino group of lysine residues in proteins to yield epsilon mono-, di-, and trimethyllysine. EC
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates.
A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed)
DNA present in neoplastic tissue.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Enzymes that catalyze the methylation of amino acids after their incorporation into a polypeptide chain. S-Adenosyl-L-methionine acts as the methylating agent. EC 2.1.1.
One of the Type II site-specific deoxyribonucleases (EC It recognizes and cleaves the sequences C/CGG and GGC/C at the slash. HpaII is from Haemophilus parainfluenzae. Several isoschizomers have been identified. EC 3.1.21.-.
A cell line derived from cultured tumor cells.
An essential amino acid. It is often added to animal feed.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.
5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The Alu sequence family (named for the restriction endonuclease cleavage enzyme Alu I) is the most highly repeated interspersed repeat element in humans (over a million copies). It is derived from the 7SL RNA component of the SIGNAL RECOGNITION PARTICLE and contains an RNA polymerase III promoter. Transposition of this element into coding and regulatory regions of genes is responsible for many heritable diseases.
Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.
RNA which does not code for protein but has some enzymatic, structural or regulatory function. Although ribosomal RNA (RNA, RIBOSOMAL) and transfer RNA (RNA, TRANSFER) are also untranslated RNAs they are not included in this scope.
The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
Formation of an acetyl derivative. (Stedman, 25th ed)
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Deoxyribonucleic acid that makes up the genetic material of plants.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.
An enzyme responsible for producing a species-characteristic methylation pattern on adenine residues in a specific short base sequence in the host cell DNA. The enzyme catalyzes the methylation of DNA adenine in the presence of S-adenosyl-L-methionine to form DNA containing 6-methylaminopurine and S-adenosyl-L-homocysteine. EC
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Established cell cultures that have the potential to propagate indefinitely.
A class of weak acids with the general formula R-CONHOH.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
A family of calcium/calmodulin-dependent PROETIN-SERINE-THREONINE KINASES. They are ubiquitously expressed in adult and embryonic mammalian tissues, and their functions are tightly related to the early stages of eukaryotic programmed cell death.
A well-characterized neutral peptide believed to be secreted by the LIVER and to circulate in the BLOOD. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on SOMATOTROPIN. It is believed to be a major fetal growth factor in contrast to INSULIN-LIKE GROWTH FACTOR I, which is a major growth factor in adults.
Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
Enzymes that catalyze the methylation of arginine residues of proteins to yield N-mono- and N,N-dimethylarginine. This enzyme is found in many organs, primarily brain and spleen.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A pyrimidine nucleoside that is composed of the base CYTOSINE linked to the five-carbon sugar D-RIBOSE.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
The protein components that constitute the common core of small nuclear ribonucleoprotein particles. These proteins are commonly referred as Sm nuclear antigens due to their antigenic nature.
The mechanisms effecting establishment, maintenance, and modification of that specific physical conformation of CHROMATIN determining the transcriptional accessibility or inaccessibility of the DNA.
Ribonucleic acid in plants having regulatory and catalytic roles as well as involvement in protein synthesis.
A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.
A family of proteins that play a role in CHROMATIN REMODELING. They are best known for silencing HOX GENES and the regulation of EPIGENETIC PROCESSES.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.
A DNA-binding protein that interacts with methylated CPG ISLANDS. It plays a role in repressing GENETIC TRANSCRIPTION and is frequently mutated in RETT SYNDROME.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in plants.
Genes whose abnormal expression, or MUTATION are associated with the development, growth, or progression of NEOPLASMS.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.
Chromosome regions that are loosely packaged and more accessible to RNA polymerases than HETEROCHROMATIN. These regions also stain differentially in CHROMOSOME BANDING preparations.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with well-defined distribution patterns in relation to time or place or both.
A glutathione transferase that catalyzes the conjugation of electrophilic substrates to GLUTATHIONE. This enzyme has been shown to provide cellular protection against redox-mediated damage by FREE RADICALS.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Morphological and physiological development of EMBRYOS.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
The turning off of GENETIC TRANSCRIPTION in certain regions of CHROMATIN without changes in the DNA sequence. Typically epigenetic repression is a way that developmental changes are programmed at the cellular level.
The human female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in humans.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
A family of histone demethylases that share a conserved Jumonji C domain. The enzymes function via an iron-dependent dioxygenase mechanism that couples the conversion of 2-oxoglutarate to succinate to the hydroxylation of N-methyl groups.
Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain.
Enzymes that catalyse the removal of methyl groups from LYSINE or ARGININE residues found on HISTONES. Many histone demethylases generally function through an oxidoreductive mechanism.
Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.
A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.
The systematic study of the complete DNA sequences (GENOME) of organisms.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC
The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION.
An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.
The genetic complement of a plant (PLANTS) as represented in its DNA.
A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed)
Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.
Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc.
Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.
A sulfur-containing essential L-amino acid that is important in many body functions.
Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.
Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Highly repeated sequences, 100-300 bases long, which contain RNA polymerase III promoters. The primate Alu (ALU ELEMENTS) and the rodent B1 SINEs are derived from 7SL RNA, the RNA component of the signal recognition particle. Most other SINEs are derived from tRNAs including the MIRs (mammalian-wide interspersed repeats).
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Tumors or cancer of the human BREAST.
Highly repetitive DNA sequences found in HETEROCHROMATIN, mainly near centromeres. They are composed of simple sequences (very short) (see MINISATELLITE REPEATS) repeated in tandem many times to form large blocks of sequence. Additionally, following the accumulation of mutations, these blocks of repeats have been repeated in tandem themselves. The degree of repetition is on the order of 1000 to 10 million at each locus. Loci are few, usually one or two per chromosome. They were called satellites since in density gradients, they often sediment as distinct, satellite bands separate from the bulk of genomic DNA owing to a distinct BASE COMPOSITION.
A thiol-containing amino acid formed by a demethylation of METHIONINE.
A dosage compensation process occurring at an early embryonic stage in mammalian development whereby, at random, one X CHROMOSOME of the pair is repressed in the somatic cells of females.
The simultaneous analysis, on a microchip, of multiple samples or targets arranged in an array format.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
Elements that are transcribed into RNA, reverse-transcribed into DNA and then inserted into a new site in the genome. Long terminal repeats (LTRs) similar to those from retroviruses are contained in retrotransposons and retrovirus-like elements. Retroposons, such as LONG INTERSPERSED NUCLEOTIDE ELEMENTS and SHORT INTERSPERSED NUCLEOTIDE ELEMENTS do not contain LTRs.
Antimetabolites that are useful in cancer chemotherapy.
A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed)
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
Enzymes that are part of the restriction-modification systems. They catalyze the endonucleolytic cleavage of DNA sequences which lack the species-specific methylation pattern in the host cell's DNA. Cleavage yields random or specific double-stranded fragments with terminal 5'-phosphates. The function of restriction enzymes is to destroy any foreign DNA that invades the host cell. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms. They are also used as tools for the systematic dissection and mapping of chromosomes, in the determination of base sequences of DNAs, and have made it possible to splice and recombine genes from one organism into the genome of another. EC 3.21.1.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.
The functional hereditary units of PLANTS.
An autosomal dominant disorder caused by deletion of the proximal long arm of the paternal chromosome 15 (15q11-q13) or by inheritance of both of the pair of chromosomes 15 from the mother (UNIPARENTAL DISOMY) which are imprinted (GENETIC IMPRINTING) and hence silenced. Clinical manifestations include MENTAL RETARDATION; MUSCULAR HYPOTONIA; HYPERPHAGIA; OBESITY; short stature; HYPOGONADISM; STRABISMUS; and HYPERSOMNOLENCE. (Menkes, Textbook of Child Neurology, 5th ed, p229)
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
An enzyme that transfers methyl groups from O(6)-methylguanine, and other methylated moieties of DNA, to a cysteine residue in itself, thus repairing alkylated DNA in a single-step reaction. EC
Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility.
The fertilized OVUM resulting from the fusion of a male and a female gamete.
Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.
Genetic mechanisms that allow GENES to be expressed at a similar level irrespective of their GENE DOSAGE. This term is usually used in discussing genes that lie on the SEX CHROMOSOMES. Because the sex chromosomes are only partially homologous, there is a different copy number, i.e., dosage, of these genes in males vs. females. In DROSOPHILA, dosage compensation is accomplished by hypertranscription of genes located on the X CHROMOSOME. In mammals, dosage compensation of X chromosome genes is accomplished by random X CHROMOSOME INACTIVATION of one of the two X chromosomes in the female.
The pattern of GENE EXPRESSION at the level of genetic transcription in a specific organism or under specific circumstances in specific cells.
A family of RNA-binding proteins that has specificity for MICRORNAS and SMALL INTERFERING RNA molecules. The proteins take part in RNA processing events as core components of RNA-induced silencing complex.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Calcium-dependent cell adhesion proteins. They are important in the formation of ADHERENS JUNCTIONS between cells. Cadherins are classified by their distinct immunological and tissue specificities, either by letters (E- for epithelial, N- for neural, and P- for placental cadherins) or by numbers (cadherin-12 or N-cadherin 2 for brain-cadherin). Cadherins promote cell adhesion via a homophilic mechanism as in the construction of tissues and of the whole animal body.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Tumors or cancer of the LUNG.
Enzymes that catalyze the S-adenosyl-L-methionine-dependent methylation of ribonucleotide bases within a transfer RNA molecule. EC 2.1.1.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Enzyme systems containing a single subunit and requiring only magnesium for endonucleolytic activity. The corresponding modification methylases are separate enzymes. The systems recognize specific short DNA sequences and cleave either within, or at a short specific distance from, the recognition sequence to give specific double-stranded fragments with terminal 5'-phosphates. Enzymes from different microorganisms with the same specificity are called isoschizomers. EC
Genes of IAP elements (a family of retrovirus-like genetic elements) which code for virus-like particles (IAPs) found regularly in rodent early embryos. ("Intracisternal" refers to the cisternae of the endoplasmic reticulum.) Under certain circumstances, such as DNA hypomethylation they are transcribed. Their transcripts are found in a variety of neoplasms, including plasmacytomas, neuroblastoma, rhabdomyosarcomas, teratocarcinomas, and colon carcinomas.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A syndrome characterized by multiple abnormalities, MENTAL RETARDATION, and movement disorders. Present usually are skull and other abnormalities, frequent infantile spasms (SPASMS, INFANTILE); easily provoked and prolonged paroxysms of laughter (hence "happy"); jerky puppetlike movements (hence "puppet"); continuous tongue protrusion; motor retardation; ATAXIA; MUSCLE HYPOTONIA; and a peculiar facies. It is associated with maternal deletions of chromosome 15q11-13 and other genetic abnormalities. (From Am J Med Genet 1998 Dec 4;80(4):385-90; Hum Mol Genet 1999 Jan;8(1):129-35)
A post-MORULA preimplantation mammalian embryo that develops from a 32-cell stage into a fluid-filled hollow ball of over a hundred cells. A blastocyst has two distinctive tissues. The outer layer of trophoblasts gives rise to extra-embryonic tissues. The inner cell mass gives rise to the embryonic disc and eventual embryo proper.
Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.
A syndrome of multiple defects characterized primarily by umbilical hernia (HERNIA, UMBILICAL); MACROGLOSSIA; and GIGANTISM; and secondarily by visceromegaly; HYPOGLYCEMIA; and ear abnormalities.
PLANTS, or their progeny, whose GENOME has been altered by GENETIC ENGINEERING.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
An enzyme which catalyzes the catabolism of S-ADENOSYLHOMOCYSTEINE to ADENOSINE and HOMOCYSTEINE. It may play a role in regulating the concentration of intracellular adenosylhomocysteine.
The process that reverts CELL NUCLEI of fully differentiated somatic cells to a pluripotent or totipotent state. This process can be achieved to a certain extent by NUCLEAR TRANSFER TECHNIQUES, such as fusing somatic cell nuclei with enucleated pluripotent embryonic stem cells or enucleated totipotent oocytes. GENE EXPRESSION PROFILING of the fused hybrid cells is used to determine the degree of reprogramming. Dramatic results of nuclear reprogramming include the generation of cloned mammals, such as Dolly the sheep in 1997.
Any method used for determining the location of and relative distances between genes on a chromosome.
An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.
A species of ascomycetous fungi of the family Sordariaceae, order SORDARIALES, much used in biochemical, genetic, and physiologic studies.
Any of the DNA in between gene-coding DNA, including untranslated regions, 5' and 3' flanking regions, INTRONS, non-functional pseudogenes, and non-functional repetitive sequences. This DNA may or may not encode regulatory functions.
Tumors or cancer of the COLON.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
Tumors or cancer of the STOMACH.
Nutritive tissue of the seeds of flowering plants that surrounds the EMBRYOS. It is produced by a parallel process of fertilization in which a second male gamete from the pollen grain fuses with two female nuclei within the embryo sac. The endosperm varies in ploidy and contains reserves of starch, oils, and proteins, making it an important source of human nutrition.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Genotypic differences observed among individuals in a population.
The formation of one or more genetically identical organisms derived by vegetative reproduction from a single cell. The source nuclear material can be embryo-derived, fetus-derived, or taken from an adult somatic cell.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.
A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12.
Methods of implanting a CELL NUCLEUS from a donor cell into an enucleated acceptor cell.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A malignant epithelial tumor with a glandular organization.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.
Nucleic acid sequences involved in regulating the expression of genes.
Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (INVERTED TANDEM REPEATS).
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.

Detailed methylation analysis of the glutathione S-transferase pi (GSTP1) gene in prostate cancer. (1/12450)

Glutathione-S-Transferases (GSTs) comprise a family of isoenzymes that provide protection to mammalian cells against electrophilic metabolites of carcinogens and reactive oxygen species. Previous studies have shown that the CpG-rich promoter region of the pi-class gene GSTP1 is methylated at single restriction sites in the majority of prostate cancers. In order to understand the nature of abnormal methylation of the GSTP1 gene in prostate cancer we undertook a detailed analysis of methylation at 131 CpG sites spanning the promoter and body of the gene. Our results show that DNA methylation is not confined to specific CpG sites in the promoter region of the GSTP1 gene but is extensive throughout the CpG island in prostate cancer cells. Furthermore we found that both alleles are abnormally methylated in this region. In normal prostate tissue, the entire CpG island was unmethylated, but extensive methylation was found outside the island in the body of the gene. Loss of GSTP1 expression correlated with DNA methylation of the CpG island in both prostate cancer cell lines and cancer tissues whereas methylation outside the CpG island in normal prostate tissue appeared to have no effect on gene expression.  (+info)

Nonmethylated transposable elements and methylated genes in a chordate genome. (2/12450)

The genome of the invertebrate chordate Ciona intestinalis was found to be a stable mosaic of methylated and nonmethylated domains. Multiple copies of an apparently active long terminal repeat retrotransposon and a long interspersed element are nonmethylated and a large fraction of abundant short interspersed elements are also methylation free. Genes, by contrast, are predominantly methylated. These data are incompatible with the genome defense model, which proposes that DNA methylation in animals is primarily targeted to endogenous transposable elements. Cytosine methylation in this urochordate may be preferentially directed to genes.  (+info)

Differential regulation of the human nidogen gene promoter region by a novel cell-type-specific silencer element. (3/12450)

Transfection analyses of the human nidogen promoter region in nidogen-producing fibroblasts from adult skin revealed multiple positive and negative cis-acting elements controlling nidogen gene expression. Characterization of the positive regulatory domains by gel mobility-shift assays and co-transfection studies in Drosophila SL2 cells unequivocally demonstrated that Sp1-like transcription factors are essential for a high expression of the human nidogen gene. Analysis of the negative regulatory domains identified a novel silencer element between nt -1333 and -1322, which is bound by a distinct nuclear factor, by using extracts from adult but not from embryonal fibroblasts. In embryonal fibroblasts, which express significantly higher amounts of nidogen mRNA as compared with adult fibroblasts, this inhibitory nidogen promoter region did not affect nidogen and SV40 promoter activities. The silencer element seems to be active only in nidogen-producing cells. Therefore this regulatory element might function in vivo to limit nidogen gene expression in response to external stimuli. However, none of the identified regulatory elements, including the silencer, contribute significantly to cell-specific expression of the human nidogen gene. Instead we provide evidence that gene expression in epidermal keratinocytes that are not producing nidogen is repressed by methylation-specific and chromatin-dependent mechanisms.  (+info)

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. (4/12450)

The DNA repair protein O6-methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the O6 position of guanine. MGMT expression is decreased in some tumor tissues, and lack of activity has been observed in some cell lines. Loss of expression is rarely due to deletion, mutation, or rearrangement of the MGMT gene, but methylation of discrete regions of the CpG island of MGMT has been associated with the silencing of the gene in cell lines. We used methylation-specific PCR to study the promoter methylation of the MGMT gene. All normal tissues and expressing cancer cell lines were unmethylated, whereas nonexpressing cancer cell lines were methylated. Among the more than 500 primary human tumors examined, MGMT hypermethylation was present in a subset of specific types of cancer. In gliomas and colorectal carcinomas, aberrant methylation was detected in 40% of the tumors, whereas in non-small cell lung carcinomas, lymphomas, and head and neck carcinomas, this alteration was found in 25% of the tumors. MGMT methylation was found rarely or not at all in other tumor types. We also analyzed MGMT expression by immunohistochemistry in relation to the methylation status in 31 primary tumors. The presence of aberrant hypermethylation was associated with loss of MGMT protein, in contrast to retention of protein in the majority of tumors without aberrant hypermethylation. Our results suggest that epigenetic inactivation of MGMT plays an important role in primary human neoplasia.  (+info)

Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggest a suppressor role in kidney, brain, and other human cancers. (5/12450)

Tissue inhibitor of metalloproteinase-3 (TIMP-3) antagonizes matrix metalloproteinase activity and can suppress tumor growth, angiogenesis, invasion, and metastasis. Loss of TIMP-3 has been related to the acquisition of tumorigenesis. Herein, we show that TIMP-3 is silenced in association with aberrant promoter-region methylation in cell lines derived from human cancers. TIMP-3 expression was restored after 5-aza-2'deoxycytidine-mediated demethylation of the TIMP-3 proximal promoter region. Genomic bisulfite sequencing revealed that TIMP-3 silencing was related to the overall density of methylation and that discrete regions within the TIMP-3 CpG island may be important for the silencing of this gene. Aberrant methylation of TIMP-3 occurred in primary cancers of the kidney, brain, colon, breast, and lung, but not in any of 41 normal tissue samples. The most frequent TIMP-3 methylation was found in renal cancers, which originate in the tissue that normally expresses the highest TIMP-3 levels. This methylation correlated with a lack of detectable TIMP-3 protein in these tumors. Together, these data show that methylation-associated inactivation of TIMP-3 is frequent in many human tumors.  (+info)

Frequent silencing of the GPC3 gene in ovarian cancer cell lines. (6/12450)

GPC3 encodes a glypican integral membrane protein and is mutated in the Simpson-Golabi-Behmel syndrome. Simpson-Golabi-Behmel syndrome, an X-linked condition, is characterized by pre- and postnatal overgrowth as well as by various other abnormalities, including increased risk of embryonal tumors. The GPC3 gene is located at Xq26, a region frequently deleted in advanced ovarian cancers. To determine whether GPC3 is a tumor suppressor in ovarian neoplasia, we studied its expression and mutational status in 13 ovarian cancer cell lines. No mutations were found in GPC3, but its expression was lost in four (31%) of the cell lines analyzed. In an of the cases where GPC3 expression was lost, the GPC3 promoter was hypermethylated, as demonstrated by Southern analysis. Expression of GPC3 was restored by treatment of the cells with the demethylating agent 5-aza-2'-deoxycytidine. A colony-forming assay confirmed that ectopic GPC3 expression inhibited the growth of ovarian cancer cell lines. Our results show that GPC3, a gene involved in the control of organ growth, is frequently inactivated in a subset of ovarian cancers and suggest that it may function as a tumor suppressor in the ovary.  (+info)

Clonality of isolated eosinophils in the hypereosinophilic syndrome. (7/12450)

The idiopathic hypereosinophilic syndrome (IHES) is a rare disorder characterized by unexplained, persistent eosinophilia associated with multiple organ dysfunction due to eosinophilic tissue infiltration. In the absence of karyotypic abnormalities, there is no specific test to detect clonal eosinophilia in IHES. Analysis of X-chromosome inactivation patterns can be used to determine whether proliferative disorders are clonal in origin. Methylation of HpaII and Hha I sites near the polymorphic trinucleotide repeat of the human androgen receptor gene (HUMARA) has been shown to correlate with X-inactivation. In this study, we have used the polymerase chain reaction (PCR) with nested primers to analyze X-inactivation patterns of the HUMARA loci in purified eosinophils from female patients with eosinophilia. Peripheral blood eosinophils were isolated by their autofluoresence using flow cytometric sorting. Eosinophils purified from a female patient presenting with IHES were found to show a clonal pattern of X-inactivation. Eosinophil-depleted leukocytes from this patient were polyclonal by HUMARA analysis, thus excluding skewedness of random X-inactivation. After corticosteroid suppression of her blood eosinophilia, a clonal population of eosinophils could no longer be detected in purified eosinophils. In contrast, eosinophils purified from a patient with Churg-Strauss syndrome and from six patients with reactive eosinophilias attributed to allergy, parasitic infection, or drug reaction showed a polyclonal pattern of X-inactivation by HUMARA analysis. The finding of clonal eosinophilia in a patient presenting with IHES indicates that such patients may have, in reality, a low-grade clonal disorder that can be distinguished from reactive eosinophilias by HUMARA analysis. Further, the method described can be used to monitor disease progression.  (+info)

Re-expression of endogenous p16ink4a in oral squamous cell carcinoma lines by 5-aza-2'-deoxycytidine treatment induces a senescence-like state. (8/12450)

We have previously reported that a set of oral squamous cell carcinoma lines express specifically elevated cdk6 activity. One of the cell lines, SCC4, contains a cdk6 amplification and expresses functional p16ink4a, the other cell lines express undetectable levels of p16ink4a, despite a lack of coding-region mutations. Two of the cell lines, SCC15 and SCC40 have a hypermethylated p16ink4A promoter and a third cell line, SCC9, has a mutation in the p16ink4a promoter. Using the demethylation agent 5-aza-2'-deoxycytidine, we showed that the p16ink4a protein was re-expressed after a 5-day treatment with this chemical. One cell line, SCC15 expressed high levels of p16ink4a. In this line, cdk6 activity was decreased after 5-aza-2'deoxycytidine treatment, and the hypophosphorylated, growth suppressive form of the retinoblastoma tumor suppressor protein pRB was detected. Expression of p16ink4a persisted, even after the drug was removed and the cells expressed senescence-associated beta-galactosidase activity. Ectopic expression of p16ink4a with a recombinant retrovirus in this cell line also induced a similar senescence-like phenotype. Hence, it was possible to restore a functional pRB pathway in an oral squamous cell carcinoma line by inducing re-expression of endogenous p16ink4a in response to treatment with a demethylating agent.  (+info)

Aim: The aim of the study was to evaluate the use of global and gene-specific DNA methylation changes as potential biomarkers for gallbladder cancer (GBC) in a cohort from Chile. Material & methods: DNA methylation was analyzed through an ELISA-based technique and quantitative methylation-specific PCR. Results: Global DNA Methylation Index (p = 0.02) and promoter methylation of SSBP2 (p = 0.01) and ESR1 (p = 0.05) were significantly different in GBC when compared with cholecystitis. Receiver curve operator analysis revealed promoter methylation of APC, CDKN2A, ESR1, PGP9.5 and SSBP2, together with the Global DNA Methylation Index, had 71% sensitivity, 95% specificity, a 0.97 area under the curve and a positive predictive value of 90%. Conclusion: Global and gene-specific DNA methylation may be useful biomarkers for GBC clinical assessment ...
Background/Purpose: Cutaneous lupus erythematous (CLE) is a disfiguring manifestation of systemic LE (SLE), and the pathogenesis remains unclear. However, epidermal regulation of skin inflammation and cell death contribute, potentially in a female-biased manner. Differential DNA methylation is important in the organ-specific manifestations of SLE but has not been studied in the skin. Thus, we explored the genome-wide DNA methylation changes in keratinocytes (KC) to investigate the functional relevance in CLE.. Methods: Eight SLE skin biopsy samples were taken from non-sun-exposed, unaffected skin from participants of the Michigan Lupus Cohort as well as age (+/- 6 years), sex, and ethnicity-matched healthy control subjects. Freshly cultured KC (at passage 2) were used to isolate DNA using DNeasy Blood and Tissue Kit. DNA was bisulfite converted for DNA methylation studies using the EZ DNA Methylation Kit. Genome-wide DNA methylation analysis was performed using the Infinium HumanMethylation450 ...
TY - JOUR. T1 - Genome-wide DNA methylation analysis reveals novel epigenetic changes in chronic lymphocytic leukemia. AU - Pei, Lirong. AU - Choi, Jeong-Hyeon. AU - Liu, Jimei. AU - Lee, Eun Joon. AU - McCarthy, Brian. AU - Wilson, James M.. AU - Speir, Ethan. AU - Awan, Farrukh. AU - Tae, Hongseok. AU - Arthur, Gerald. AU - Schnabel, Jennifer L.. AU - Taylor, Kristen H.. AU - Wang, Xinguo. AU - Xu, Dong. AU - Ding, Hanfei. AU - Munn, David H. AU - Caldwell, Charles W.. AU - Shi, Huidong. PY - 2012/6. Y1 - 2012/6. N2 - We conducted a genome-wide DNA methylation analysis in CD19+ B-cells from chronic lymphocytic leukemia (CLL) patients and normal control samples using reduced representation bisulfite sequencing (RRBS). The methylation status of 1.8-2.3 million CpGs in the CLL genome was determined; about 45% of these CpGs were located in more than 23,000 CpG islands (CGIs). While global CpG methylation was similar between CLL and normal B-cells, 1,764 gene promoters were identified as being ...
Human cancers almost ubiquitously harbor epigenetic alterations. Although such alterations in epigenetic marks, including DNA methylation, are potentially heritable, they can also be dynamically altered. Given this potential for plasticity, the degree to which epigenetic changes can be subject to selection and act as drivers of neoplasia has been questioned. We carried out genome-scale analyses of DNA methylation alterations in lethal metastatic prostate cancer and created DNA methylation cityscape plots to visualize these complex data. We show that somatic DNA methylation alterations, despite showing marked interindividual heterogeneity among men with lethal metastatic prostate cancer, were maintained across all metastases within the same individual. The overall extent of maintenance in DNA methylation changes was comparable to that of genetic copy number alterations. Regions that were frequently hypermethylated across individuals were markedly enriched for cancer- and ...
TY - CHAP. T1 - Computational Approaches in Next-Generation Sequencing Data Analysis for Genome-Wide DNA Methylation Studies. AU - Choi, Jeong Hyeon. AU - Shi, Huidong. PY - 2016/9/6. Y1 - 2016/9/6. N2 - DNA methylation is one of the most important epigenetic mechanisms that ensures the maintenance and inheritance of gene-expression programs in mammalian cells. Three highly conserved DNA methyltransferase (DNMT) proteins (DNMT1, DNMT3A, and DNMT3B), which complex together in vivo, establish and maintain the DNA methylation landscape within the human genome. These novel next-generation sequencing (NGS) platforms also have many other advantages over the current platforms such as less bias during template preparation, possible longer read length, lower cost, higher speed, and better accuracy. The chapter presents the enrichment-based sequencing and bisulfite treatment-based approaches have successfully profiled DNA methylation and identified genome-wide differential methylation. The DMRs are ...
Cancer Epigenetics: An Introduction -- Community Resources and Technologies Developed Through the NIH Roadmap Epigenomics Program -- Epigenome-Wide Association Studies (EWAS): Past, Present, and Future -- Epigenetic Biomarkers in Liver Cancer -- Cancer Type Specific Epigenetic Changes: Gastric Cancer -- Beyond the Island: Epigenetic Biomarkers of Colorectal and Prostate Cancer -- Prostate Cancer Epigenome -- CpG Island Hypermethylation as a Biomarker for the Early Detection of Lung Cancer -- Analysis of DNA Methylation in Pancreatic Cancer: An Update -- Epigenetics of Urothelial Carcinoma -- Epigenetics of Prostate Cancer -- Methylation Profile Landscape in Mesothelioma: Possible Implications in Early Detection, Disease Progression, and Therapeutic Options -- Techniques to Access Histone Modifications and Variants in Cancer -- Single Base Resolution Analysis of 5-Methylcytosine and 5-Hydroxymethylcytosine by RRBS and TAB-RRBS -- Quantitative DNA Methylation Analysis for Epigenotyping of ...
TY - JOUR. T1 - Quantitative DNA methylation analysis detects cervical intraepithelial neoplasms type 3 and worse. AU - Lai, Hung Cheng. AU - Lin, Ya Wen. AU - Huang, Rui Lan. AU - Chung, Ming Tzeung. AU - Wang, Hui Chen. AU - Liao, Yu Ping. AU - Su, Po Hsuan. AU - Liu, Yung Liang. AU - Yu, Mu Hsien. PY - 2010/9/15. Y1 - 2010/9/15. N2 - BACKGROUND: DNA methylation may be used a potential biomarker for detecting cervical cancer. The authors of this report used quantitative methylation analysis of 4 genes in a full spectrum of cervical lesions to test its potential clinical application. METHODS: This hospital-based, retrospective, case-control study was conducted in 185 patients and included patients who had a normal uterine cervix (n = 53), cervical intraepithelial neoplasm type 1 (CIN1) (n = 37), CIN2 (n = 22), CIN3 (n = 24), carcinoma in situ (CIS) (n = 22), squamous cell carcinoma (SCC, n = 20), and adenocarcinoma (AC) (n = 7). Methylation levels of the genes sex-determining region Y, box 1 ...
Early life is a period of drastic epigenetic remodeling in which the epigenome is especially sensitive to extrinsic and intrinsic influence. However, the epigenome-wide dynamics of the DNA methylation changes that occur during this period have not been sufficiently characterized in longitudinal studies. To this end, we studied the DNA methylation status of more than 750,000 CpG sites using Illumina MethylationEPIC arrays on 33 paired blood samples from 11 subjects at birth and at 5 and 10 years of age, then characterized the chromatin context associated with these loci by integrating our data with histone, chromatin-state and enhancer-element external datasets, and, finally, validated our results through bisulfite pyrosequencing in two independent longitudinal cohorts of 18 additional subjects. We found abundant DNA methylation changes (110,726 CpG sites) during the first lustrum of life, while far fewer alterations were observed in the subsequent 5 years (460 CpG sites). However, our analysis revealed
TY - JOUR. T1 - Association of DNA methylation differences with schizophrenia in an epigenome-wide association study. AU - Montano, Carolina. AU - Taub, Margaret Anne. AU - Jaffe, Andrew. AU - Briem, Eirikur. AU - Feinberg, Jason I.. AU - Trygvadottir, Rakel. AU - Idrizi, Adrian. AU - Runarsson, Arni. AU - Berndsen, Birna. AU - Gur, Ruben C.. AU - Moore, Tyler M.. AU - Perry, Rodney T.. AU - Fugman, Doug. AU - Sabunciyan, Sarven. AU - Yolken, Robert H. AU - Hyde, Thomas. AU - Kleinman, Joel. AU - Sobell, Janet L.. AU - Pato, Carlos N.. AU - Pato, Michele T.. AU - Go, Rodney C.. AU - Nimgaonkar, Vishwajit. AU - Weinberger, Daniel. AU - Braff, David. AU - Gur, Raquel E.. AU - Fallin, Daniele Daniele. AU - Feinberg, Andrew P. PY - 2016/5/1. Y1 - 2016/5/1. N2 - Importance: DNA methylation may play an important role in schizophrenia (SZ), either directly as a mechanism of pathogenesis or as a biomarker of risk. O. Objective: To scan genome-wide DNA methylation data to identify differentially ...
TY - JOUR. T1 - Differences in Genome-wide DNA Methylation Profiles in Breast Milk by Race and Lactation Duration. AU - Davis Lynn, Brittny C.. AU - Bodelon, Clara. AU - Pfeiffer, Ruth M.. AU - Yang, Hannah P.. AU - Yang, Howard H.. AU - Lee, Maxwell. AU - Laird, Peter W.. AU - Campan, Mihaela. AU - Weisenberger, Daniel J.. AU - Murphy, Jeanne. AU - Sampson, Joshua N.. AU - Browne, Eva P.. AU - Anderton, Douglas L.. AU - Sherman, Mark E.. AU - Arcaro, Kathleen F.. AU - Gierach, Gretchen L.. PY - 2019. Y1 - 2019. N2 - Black women in the United States are disproportionately affected by early-onset, triple-negative breast cancer. DNA methylation has shown differences by race in healthy and tumor breast tissues. We examined associations between genome-wide DNA methylation levels in breast milk and breast cancer risk factors, including race, to explain how this reproductive stage influences a womans risk for, and potentially contributes to racial disparities in, breast cancer. Breast milk samples ...
TY - JOUR. T1 - Relationship of the aberrant DNA hypermethylation of cancer-related genes with carcinogenesis of endometrial cancer. AU - Banno, Kouji. AU - Yanokura, Megumi. AU - Susumu, Nobuyuki. AU - Kawaguchi, Makiko. AU - Hirao, Nobumaru. AU - Hirasawa, Akira. AU - Tsukazaki, Katsumi. AU - Aoki, Daisuke. PY - 2006/12/1. Y1 - 2006/12/1. N2 - Epigenetic abnormalities including the aberrant DNA hypermethylation of the promoter CpG islands play a key role in the mechanism of gene inactivation in cell carcinogenesis. To identify the genes associated with aberrant DNA hypermethylation in endometrial carcinogenesis, we studied the hypermethylation of the promoter regions of five genes: hMLH1, APC, E-cadherin, RAR-β and p16. The frequencies of aberrant hypermethylation were 40.4% (21/52) in hMLH1, 22% (11/50) in APC, 14% (7/50) in E- cadherin, and 2.3% (1/44) in RAR-β in endometrial cancer specimens. No aberrant DNA methylation was found in p16. In atypical endometrial hyperplasia, the ...
Context: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. Objective: The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort. Design: Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Setting: MS-MLPA was performed in a training cohort of 50 patients with ACC to identify the best set of probes correlating with disease-free survival (DFS) and overall survival (OS). These outcomes were validated in an independent cohort from 21 ENSAT centers. Patients: The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors). Main Outcome Measures: DFS and OS. Results: In the training cohort, mean methylation of 4
Panic disorder (PD) is considered to be a multifactorial disorder emerging from interactions among multiple genetic and environmental factors. To date, although genetic studies reported several susceptibility genes with PD, few of them were replicated and the pathogenesis of PD remains to be clarified. Epigenetics is considered to play an important role in etiology of complex traits and diseases, and DNA methylation is one of the major forms of epigenetic modifications. In this study, we performed an epigenome-wide association study of PD using DNA methylation arrays so as to investigate the possibility that different levels of DNA methylation might be associated with PD. The DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N = 48, control, N = 48) extracted from peripheral blood. Methylation arrays were used for the analysis. β values, which represent the levels of DNA methylation, were normalized via an appropriate pipeline. Then, β values were
TY - JOUR. T1 - Minimal evidence for consistent changes in maize DNA methylation patterns following environmental stress. AU - Eichten, Steven R.. AU - Springer, Nathan M.. PY - 2015/5/30. Y1 - 2015/5/30. N2 - DNA methylation is a chromatin modification that is sometimes associated with epigenetic regulation of gene expression. As DNA methylation can be reversible at some loci, it is possible that methylation patterns may change within an organism that is subjected to environmental stress. In order to assess the effects of abiotic stress on DNA methylation patterns in maize (Zea mays), seeding plants were subjected to heat, cold, and UV stress treatments. Tissue was later collected from individual adult plants that had been subjected to stress or control treatments and used to perform DNA methylation profiling to determine whether there were consistent changes in DNA methylation triggered by specific stress treatments. DNA methylation profiling was performed by immunoprecipitation of methylated ...
There is growing interest in the role of DNA methylation in regulating the transcription of mitochondrial genes, particularly in brain disorders characterized by mitochondrial dysfunction. However, to date a genome-wide, high-resolution analysis of the mitochondrial DNA methylome has yet to be undertaken. We have used a novel approach to interrogate the mitochondrial DNA methylome at single base resolution using targeted bisulfite sequencing. We applied this method to investigate mitochondrial DNA methylation patterns in post-mortem superior temporal gyrus and cerebellum brain tissue from seven human donors. Here you can explore mitochondria DNA methylation levels in superior temporal gyrus and cerebellum tissue along UCSC tracks. Mitochondrial DNA methylation patterns are relatively low but conserved, with peaks in DNA methylation ,5% at a number of sites, such as within the D-LOOP and MT-ND5 and higher levels of methylation at non-CpG compared to CpG sites.. ...
Lung cancer is the leading cause of cancer death in men and women in the United States and Western Europe. Over 160,000 Americans die of this disease every year. The five-year survival rate is 15% - significantly lower than that of other major cancers. Early detection is a key factor in increasing lung cancer patient survival. DNA hypermethylation is recognized as an important mechanism for tumor suppressor gene inactivation in cancer and could yield powerful biomarkers for early detection of lung cancer. Here we focused on developing DNA methylation markers for squamous cell carcinoma of the lung. Using the sensitive, high-throughput DNA methylation analysis technique MethyLight, we examined the methylation profile of 42 loci in a collection of 45 squamous cell lung cancer samples and adjacent non-tumor lung tissues from the same patients. We identified 22 loci showing significantly higher DNA methylation levels in tumor tissue than adjacent non-tumor lung. Of these, eight showed highly significant
TY - JOUR. T1 - Regulation and function of DNA methylation in plants and animals. AU - He, Xinjian. AU - Chen, Taiping. AU - Zhu, Jian-Kang. N1 - KAUST Repository Item: Exported on 2020-10-01 Acknowledgements: This work was supported by the National Institutes of Health grants R01GM070795 and R01GM059138 to J-KZ.. PY - 2011/2/15. Y1 - 2011/2/15. N2 - DNA methylation is an important epigenetic mark involved in diverse biological processes. In plants, DNA methylation can be established through the RNA-directed DNA methylation pathway, an RNA interference pathway for transcriptional gene silencing (TGS), which requires 24-nt small interfering RNAs. In mammals, de novo DNA methylation occurs primarily at two developmental stages: during early embryogenesis and during gametogenesis. While it is not clear whether establishment of DNA methylation patterns in mammals involves RNA interference in general, de novo DNA methylation and suppression of transposons in germ cells require 24-32-nt ...
Colorectal cancer (CRC) is characterized by genome-wide alterations to DNA methylation that influence gene expression and genomic stability. Less is known about the extent to which methylation is disrupted in the earliest stages of CRC development. In this study, we have combined laser-capture microdissection with reduced representation bisulfite sequencing to identify cancer-associated DNA methylation changes in human aberrant crypt foci (ACF), the earliest putative precursor to CRC. Using this approach, methylation profiles have been generated for 10 KRAS-mutant ACF and 10 CRCs harboring a KRAS mutation, as well as matched samples of normal mucosa. Of 811 differentially methylated regions (DMRs) identified in ACF, 537 (66%) were hypermethylated and 274 (34%) were hypomethylated. DMRs located within intergenic regions were heavily enriched for AP-1 transcription factor binding sites and were frequently hypomethylated. Furthermore, gene ontology analysis demonstrated that DMRs associated with promoters
Cardiac disease modelling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) requires thorough insight into cardiac cell type differentiation processes. However, current methods to discriminate different cardiac cell types are mostly time-consuming, are costly and often provide imprecise phenotypic evaluation. DNA methylation plays a critical role during early heart development and cardiac cellular specification. We therefore investigated the DNA methylation pattern in different cardiac tissues to identify CpG loci for further cardiac cell type characterization. An array-based genome-wide DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChips led to the identification of 168 differentially methylated CpG loci in atrial and ventricular human heart tissue samples (n = 49) from different patients with congenital heart defects (CHD). Systematic evaluation of atrial-ventricular DNA methylation pattern in cardiac tissues in an independent sample cohort of non
Foret, S; Kucharski, R; Pellegrini, M; Feng, S; Jacobsen, SE; Robinson, GE and Maleszka, R (2012) DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey bees. Proceedings of the National Academy of Sciences of the United States of America. 109(13): 4968-4973 ...
Prostate cancer (PC) is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181) and the GABRE~miR-452~miR-224 ...
TY - JOUR. T1 - Diagnostic markers of urothelial cancer based on DNA methylation analysis. AU - Chihara, Yoshitomo. AU - Kanai, Yae. AU - Fujimoto, Hiroyuki. AU - Sugano, Kokichi. AU - Kawashima, Kiyotaka. AU - Liang, Gangning. AU - Jones, Peter A.. AU - Fujimoto, Kiyohide. AU - Kuniyasu, Hiroki. AU - Hirao, Yoshihiko. PY - 2013. Y1 - 2013. N2 - BACKGROUND: Early detection and risk assessment are crucial for treating urothelial cancer (UC), which is characterized by a high recurrence rate, and necessitates frequent and invasive monitoring. We aimed to establish diagnostic markers for UC based on DNA methylation.METHODS: In this multi-center study, three independent sample sets were prepared. First, DNA methylation levels at CpG loci were measured in the training sets (tumor samples from 91 UC patients, corresponding normal-appearing tissue from these patients, and 12 normal tissues from age-matched bladder cancer-free patients) using the Illumina Golden Gate methylation assay to identify ...
Our current view of DNA methylation processes is strongly moving: First, even if it was generally admitted that DNMT3A and DNMT3B are associated with de novo methylation and DNMT1 is associated with inheritance DNA methylation, these distinctions are now not so clear. Secondly, since one decade, many partners of DNMTs have been involved in both the regulation of DNA methylation activity and DNMT recruitment on DNA. The high diversity of interactions and the combination of these interactions let us to subclass the different DNMT-including complexes. For example, the DNMT3L/DNMT3A complex is mainly related to de novo DNA methylation in embryonic states, whereas the DNMT1/PCNA/UHRF1 complex is required for maintaining global DNA methylation following DNA replication. On the opposite to these unspecific DNA methylation machineries (no preferential DNA sequence), some recently identified DNMT-including complexes are recruited on specific DNA sequences. The coexistence of both types of DNA methylation (un
Type 2 diabetes mellitus (T2D) is a slowly progressive disease that can be postponed or even avoided through lifestyle changes. Recent data demonstrate highly significant correlations between DNA methylation and the most important risk factors of T2D, including age and BMI, in blood and human tissues relevant to insulin resistance and T2D. Also, T2D patients and individuals with increased risk of the disease display differential DNA methylation profiles and plasticity compared to controls. Accordingly, the novel clues to DNA methylation fingerprints in blood and tissues with deteriorated metabolic capacity indicate that blood-borne epigenetic biomarkers of T2D progression might become a reality. This Mini Review will address the most recent associations between DNA methylation and diabetes-related traits in human tissues and blood. The overall focus is on the potential of future epigenome-wide studies, carried out across tissues and populations with correlations to pre-diabetes and T2D risk factors, to
TY - JOUR. T1 - Peripheral blood DNA methylation differences in twin pairs discordant for Alzheimers disease. AU - Konki, Mikko. AU - Malonzo, Maia. AU - K Karlsson, Ida. AU - Lindgren, Noora. AU - Ghimire, Bishwa. AU - Smolander, Johannes. AU - M Scheinin, Noora. AU - Ollikainen, Miina. AU - Laiho, Asta. AU - L Elo, Laura. AU - Lönnberg, Tapio. AU - Röyttä, Matias. AU - Pedersen, Nancy L.. AU - Kaprio, Jaakko. AU - Lähdesmäki, Harri. AU - O Rinne, Juha. AU - J Lund, Riikka. PY - 2019. Y1 - 2019. N2 - Background Alzheimers disease results from a neurodegenerative process that starts well before the diagnosis can be made. New prognostic or diagnostic markers enabling early intervention into the disease process would be highly valuable. Environmental and lifestyle factors largely modulate the disease risk and may influence the pathogenesis through epigenetic mechanisms, such as DNA methylation. As environmental and lifestyle factors may affect multiple tissues of the body, we hypothesized ...
Maintaining and acquiring the pluripotent cell state in plants is critical to tissue regeneration and vegetative multiplication. Histone-based epigenetic mechanisms are important for regulating this undifferentiated state. Here we report the use of genetic and pharmacological experimental approaches to show that Arabidopsis cell suspensions and calluses specifically repress some genes as a result of promoter DNA hypermethylation. We found that promoters of the MAPK12, GSTU10 and BXL1 genes become hypermethylated in callus cells and that hypermethylation also affects the TTG1, GSTF5, SUVH8, fimbrin and CCD7 genes in cell suspensions. Promoter hypermethylation in undifferentiated cells was associated with histone hypoacetylation and primarily occurred at CpG sites. Accordingly, we found that the process specifically depends on MET1 and DRM2 methyltransferases, as demonstrated with DNA methyltransferase mutants. Our results suggest that promoter DNA methylation may be another important epigenetic ...
The incidence of cervical adenocarcinoma (CA) is rising, whereas the incidence of cervical squamous cell carcinoma (CSCC) continues to decrease. However, it is still unclear whether different molecular characteristics underlie these 2 types of cervical carcinoma. To better understand the epigenetic characteristics of cervical carcinoma, we investigated the DNA promoter hypermethylation profiles in CA and CSCC. In addition, we investigated whether DNA hypermethylation patterns might be used for the molecular diagnosis of CA and endometrial adenocarcinoma (EA). Using the bisulfite-modification technique and methylation-specific PCR, we examined the aberrant promoter hypermethylation patterns of 9 tumor suppressor genes (APC, DAPK, CDH1, HLTF, hMLH1, p16, RASSF1A, THBS1 and TIMP3) in 62 CSCCs, 30 CAs and 21 EAs. After Bonferroni correction adjustment (statistically significant at p , 0.0055), we found that the aberrant hypermethylations of CDH1 and DAPK were more frequent in CSCCs than in CAs ...
Similar to most cancers, genome-wide DNA methylation profiles are commonly altered in pediatric acute lymphoblastic leukemia (ALL); however, recent observations highlight that a large portion of malignancy-associated DNA methylation alterations are not accompanied by related gene expression changes. By analyzing and integrating the methylome and transcriptome profiles of pediatric B-cell ALL cases and primary tissue controls, we report 325 genes hypermethylated and downregulated and 45 genes hypomethylated and upregulated in pediatric B-cell ALL, irrespective of subtype. Repressed cation channel subunits and cAMP signaling activators and transducers are overrepresented, potentially indicating a reduced cellular potential to receive and propagate apoptotic signals. Furthermore, we report specific DNA methylation alterations with concurrent gene expression changes within individual ALL subtypes. The ETV6-RUNX1 translocation was associated with downregulation of ASNS and upregulation of the ...
It is widely known that maternal physical exercise is able to induce beneficial improvements in offspring cognition; however, the effects of paternal exercise have not been explored in detail. The present study was designed to evaluate the impact of paternal physical exercise on memory and learning, neuroplasticity and DNA methylation levels in the hippocampus of male offspring. Adult male Wistar rats were divided into two groups: sedentary or exercised fathers. The paternal preconception exercise protocol consisted of treadmill running, 20 minutes daily, 5 consecutive days per week for 22 days, while the mothers were not trained. After mating, paternal sperm was collected for global DNA methylation analysis. At postnatal day 53, the offspring were euthanized, and the hippocampus was dissected to measure cell survival by 5-bromo-2′-deoxiuridine and to determine the expression of synaptophysin, reelin, brain-derived neurotrophic factor and global DNA methylation levels. To measure spatial ...
Genome-wide hypomethylation is a hallmark of many cancers and is thought to contribute to tumorigenesis independently of CpG island hypermethylation ( 9, 33, 37). Expanding on early observations from a very limited number of gliomas ( 5, 38), we found that genomic hypomethylation occurs at a high frequency in GBM and GBM cell lines. Interestingly, global hypomethylation was not observed in two primary GBMs, indicating that a small proportion of GBMs may arise in the absence of extensive demethylation, although these two tumors exhibit clear differences in genetic and proliferative characteristics relative to severely hypomethylated tumors. However, the whole-genome approach to quantify DNA methylation is not sufficiently sensitive to detect potentially important regional reductions in 5-methylcytosine that can contribute to genomic instability. The high prevalence of genomic hypomethylation in GBM supports an important role for 5-methylcytosine reduction in GBM pathology.. Global decreases in ...
TY - JOUR. T1 - Comparison of different normalization assumptions for analyses of DNA methylation data from the cancer genome. AU - Wang, Dong. AU - Zhang, Yuannv. AU - Huang, Yan. AU - Li, Pengfei. AU - Wang, Mingyue. AU - Wu, Ruihong. AU - Cheng, Lixin. AU - Zhang, Wenjing. AU - Zhang, Yujing. AU - Li, Bin. AU - Wang, Chenguang. AU - Guo, Zheng. PY - 2012/9/10. Y1 - 2012/9/10. N2 - Nowadays, some researchers normalized DNA methylation arrays data in order to remove the technical artifacts introduced by experimental differences in sample preparation, array processing and other factors. However, other researchers analyzed DNA methylation arrays without performing data normalization considering that current normalizations for methylation data may distort real differences between normal and cancer samples because cancer genomes may be extensively subject to hypomethylation and the total amount of CpG methylation might differ substantially among samples. In this study, using eight datasets by ...
To demonstrate the presence of CpG island methylation in these 27 up-regulated miRNAs, we undertook bisulfite genomic sequencing analyses of multiple clones in the metastatic cancer cell from which the miRNA expression microarray data were obtained. We found dense CpG island hypermethylation in 16 (59%) of the described miRNAs (Fig. 1A and Table S2). We wanted to focus on the cancer-specific DNA methylation changes, so we used bisulfite genomic sequencing to analyze the DNA methylation status of these 16 miRNAs in normal tissues (n = 32), including colorectal mucosa, lymphocytes, and skin, to exclude tissue-specific DNA methylation patterns. The expression of many miRNAs is tightly regulated according to cell type (1, 2), so it was not surprising to observe that 11 (65%) of the miRNAs were also densely methylated in normal tissues (Fig. 1A, Table S2, and Fig. S1). The previously mentioned miR-126 was one of these. However, and most importantly, miR148a, miR-34b/c, miR-9-1, miR-9-2, and miR-9-3 ...
TY - JOUR. T1 - Two-stage Genome-wide Methylation Profiling in Childhood-onset Crohns Disease Implicates Epigenetic Alterations at the VMP1/MIR21 and HLA Loci. AU - Adams, Alex T. AU - Kennedy, Nicholas A. AU - Hansen, Richard. AU - Ventham, Nicholas T. AU - OʼLeary, Kate R. AU - Drummond, Hazel E. AU - Noble, Colin L. AU - El-Omar, Emad. AU - Russell, Richard K. AU - Wilson, David C. AU - Nimmo, Elaine R. AU - Hold, Georgina L. AU - Satsangi, Jack. PY - 2014/10. Y1 - 2014/10. N2 - BACKGROUND: As a result of technological and analytical advances, genome-wide characterization of key epigenetic alterations is now feasible in complex diseases. We hypothesized that this may provide important insights into gene-environmental interactions in Crohns disease (CD) and is especially pertinent to early onset disease.METHODS: The Illumina 450K platform was applied to assess epigenome-wide methylation profiles in circulating leukocyte DNA in discovery and replication pediatric CD cohorts and controls. ...
Abnormal DNA methylation patterns have been demonstrated to be associated with the pathogenesis of Alzheimers disease (AD). The present study aimed to identify differential methylation in the superior temporal gyrus (STG) of patients with late‑onset AD based on epigenome‑wide DNA methylation data by bioinformatics analysis. The genome‑wide DNA methylation data in the STG region of 34 patients with late‑onset AD and 34 controls without dementia were recruited from the Gene Expression Omnibus database. Through systemic quality control, differentially methylated CpG sites were determined by the Students t‑test and mean methylation value differences between the two conditions. Hierarchical clustering analysis was applied to assess the classification performance of differentially methylated CpGs. Functional analysis was performed to investigate the biological functions of the genes associated with differentially methylated CpGs. A total of 17,895 differentially methylated CpG sites were ...
The potential influence of underlying differences in relative leukocyte distributions in studies involving blood-based profiling of DNA methylation is well recognized and has prompted development of a set of statistical methods for inferring changes in the distribution of white blood cells using DNA methylation signatures. However, the extent to which this methodology can accurately predict cell type proportions based on blood-derived DNA methylation data in a large-scale epigenome-wide association study (EWAS) has yet to be examined. We used publicly available data deposited in the Gene Expression Omnibus (GEO) database (accession no. GSE37008), which consisted of both blood-derived epigenome-wide DNA methylation data assayed using the Illumina Infinium HumanMethylation27 BeadArray and complete blood cell (CBC) counts among a community cohort of 94 non-diseased individuals. Constrained projection (CP) was used to obtain predictions of the proportions of lymphocytes, monocytes, and granulocytes ...
DNA methylation (global and gene-specific) has been reported as an epigenetic mechanism that could be involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Furthermore, epigenetic therapy has been suggested as a future possibility for T2DM treatment. Epigenetic changes illustrate the environmental link of the disease. Since some of the epigenetic modifications can be reversed, they could be used as potential therapeutic targets. The aim of the systematic review will be to synthesise the available evidence pertaining to the link between DNA methylation and T2DM. The systematic review will evaluate characteristics of reported studies such as the source of DNA used, methods of quantifying DNA methylation and the participants demographics (age, gender, race and adiposity). We will conduct a narrative synthesis of data, and if there are an adequate number of sufficiently homogenous studies, we will consider performing a meta-analysis. The review will evaluate if the levels of DNA methylation are
BACKGROUND: The association of in vitro fertilisation (IVF) and DNA methylation has been studied predominantly at regulatory regions of imprinted genes and at just thousands of the ~28 million CpG sites in the human genome. METHODS: We investigated the links between IVF and DNA methylation patterns in whole cord blood cells (n = 98) and cord blood mononuclear cells (n = 82) from newborn twins using genome-wide methylated DNA immunoprecipitation coupled with deep sequencing. RESULTS: At a false discovery rate (FDR) of 5%, we identified one significant whole blood DNA methylation change linked to conception via IVF, which was located ~3 kb upstream of TNP1, a gene previously linked to male infertility. The 46 most strongly associated signals (FDR of 25%) included a second region in a gene also previously linked to infertility, C9orf3, suggesting that our findings may in part capture the effect of parental subfertility. Using twin modelling, we observed that individual-specific environmental ...
DNA methylation-based biomarkers were suggested to be promising for early cancer diagnosis. However, DNA methylation-based biomarkers for esophageal squamous cell carcinoma (ESCC), especially in Chinese Han populations have not been identified and evaluated quantitatively. To identify the candidate DNA-methylation based biomarkers for ESCC diagnosis, we performed the targeted bisulfite sequencing analysis in this study. Based on these 94 pairs of ESCC tumors and adjacent normal tissues, we found out that ADHFE1, EOMES, SALL1 and TFPI2 could be an effective methylation-based assay for ESCC diagnosis. ...
BackgroundRenal cell carcinoma (RCC) is the tenth most commonly diagnosed cancer in the United States. While it is usually lethal when metastatic, RCC is successfully treated with surgery when tumors are confined to the kidney and have low tumor volume. Because most early stage renal tumors do not result in symptoms, there is a strong need for biomarkers that can be used to detect the presence of the cancer as well as to monitor patients during and after therapy.MethodsWe examined genome-wide DNA methylation alterations in renal cell carcinomas of diverse histologies and benign adjacent kidney tissues from 96 patients.ResultsWe observed widespread methylation differences between tumors and benign adjacent tissues, particularly in immune-, G-protein coupled receptor-, and metabolism-related genes. Additionally, we identified a single panel of DNA methylation biomarkers that reliably distinguishes tumor from benign adjacent tissue in all of the most common kidney cancer histologic subtypes, and a ...
In recent years several methods have been developed to provide a genome-wide picture of the state of DNA methylation, including: next-generation genome-wide sequencing of bisulfite-converted DNA [8]; methylated DNA immunoprecipitation (MeDIP) followed by either hybridization to high-density oligonucleotide arrays [84] or next-generation sequencing [85]; and dedicated Illumina 27 K and 450 K arrays [86] that measure the state of methylation of well characterized CG sites distributed in the genome. Although genome-wide sequencing is still prohibitively costly for large population studies, array approaches are being frequently used to delineate DNA methylation signatures of disease states in primary clinical material rather than cell lines. Several studies have used this approach to differentiate breast cancer subtypes and their prognosis. Li et al. [87] used 27 K arrays in a small sample of ER/PR+ and ER/PR- breast cancer samples, and identified and validated four genes whose DNA methylation was ...
Perturbation of DNA methylation is frequent in cancers and has emerged as an important mechanism involved in tumorigenesis. To determine how DNA methylation is modified in the genome of primary glioma, we used Methyl-DNA immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays to identify differentially DNA methylation sequences between primary glioma and normal brain tissue samples. MeDIP-chip technology was used to investigate the whole-genome differential methylation patterns in glioma and normal brain tissues. Subsequently, the promoter methylation status of eight candidate genes was validated in 40 glioma samples and 4 cell lines by Sequenoms MassARRAY system. Then, the epigenetically regulated expression of these genes and the potential mechanisms were examined by chromatin immunoprecipitation and quantitative real-time PCR. A total of 524 hypermethylated and 104 hypomethylated regions were identified in glioma. Among them, 216 hypermethylated and 60 hypomethylated regions were mapped
1. Maegawa S, Hinkal G, Kim HS, Shen L, Zhang L, et al. (2010) Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res 20: 332-340. doi: 10.1101/gr.096826.109 20107151. 2. Teschendorff AE, Menon U, Gentry-Maharaj A, Ramus SJ, Weisenberger DJ, et al. (2010) Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res 20: 440-446. doi: 10.1101/gr.103606.109 20219944. 3. Rakyan VK, Down TA, Maslau S, Andrew T, Yang TP, et al. (2010) Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res 20: 434-439. doi: 10.1101/gr.103101.109 20219945. 4. Heyn H, Li N, Ferreira HJ, Moran S, Pisano DG, et al. (2012) Distinct DNA methylomes of newborns and centenarians. Proceedings of the National Academy of Sciences.. 5. Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, et al. (2013) Genome-wide methylation profiles reveal quantitative views of human aging rates. Mol Cell 49: 359-67. doi: ...
TY - CHAP. T1 - DNA Methylation Alterations in Human Cancers. AU - Kanai, Yae. AU - Arai, Eri. PY - 2012. Y1 - 2012. UR - UR - U2 - 10.1016/B978-0-12-388415-2.00003-2. DO - 10.1016/B978-0-12-388415-2.00003-2. M3 - Chapter. AN - SCOPUS:84882534159. SN - 9780123884152. SP - 29. EP - 52. BT - Epigenetics in Human Disease. PB - Elsevier Inc.. ER - ...
View more ,Stunting in children is a global public health concern. We investigated how global DNA methylation relates to food intakes, dietary diversity, and development of stunting among 324 children aged 24-36 months in a slum community in Dhaka, Bangladesh. Stunted children (height-for-age z score ˂-2; n = 162) and their age- and sex-matched nonstunted counterparts (height-for-age z score ˃-1; n = 162) were selected by active community surveillance. We studied global DNA methylation, measured as 5-mC% content in whole blood. Dietary intake, anthropometric measurement, and sociodemographic information were obtained. In the multiple linear regression model, increased global DNA methylation level in children was significantly associated with consumption of lower amount of energy, coef: .034 (95% CI [.014, .053]); P = .001, protein, coef: .038 (95% CI [.019, .057]); P = .000, carbohydrate, coef: .027 (95% CI [.008, .047]); P = .006, zinc, coef: .020 (95% CI [.001, .039]); P = .043, total ...
immune Uncategorized IL12RB1, Tropanserin Although aberrant DNA methylation patterning is normally a hallmark of cancer the relevance of targeting DNA methyltransferases (DNMT) remains unclear for some Tropanserin tumors. chemosensitization and demethylation delineating a personalized technique for the clinical usage of DNMTIs. Tropanserin in non-Hodgkin lymphomas (NHL)(2) a meeting associated with even more intense variants of the condition(3). Inactivation of tumor suppressor pathways can be an essential contributor to level of resistance to chemotherapy in cancers(4-6) partly as the activity of all chemotherapy realtors depends to an excellent extent on a single pro-apoptotic and pro-differentiation pathways that are impaired during carcinogenesis. Inactivation of the pathways by Tropanserin mutations or hypermethylation can as a result affect drug awareness(4 7 Gene particular and genomic modifications in DNA methylation have already been described in the many subtypes of NHL(8-14). ...
DNA methylation plays crucial roles in most eukaryotic organisms. Bisulfite sequencing (BS-Seq) is a sequencing approach that provides quantitative cytosine methylation levels in genome-wide scope and single-base resolution. However, genomic variations such as insertions and deletions (indels) affect methylation calling, and the alignment of reads near/across indels becomes inaccurate in the presence of polymorphisms. Hence, the simultaneous detection of DNA methylation and indels is important for exploring the mechanisms of functional regulation in organisms. These problems motivated us to develop the algorithm BatMeth2, which can align BS reads with high accuracy while allowing for variable-length indels with respect to the reference genome. The results from simulated and real bisulfite DNA methylation data demonstrated that our proposed method increases alignment accuracy. Additionally, BatMeth2 can calculate the methylation levels of individual loci, genomic regions or functional regions such as
DNA methylation is an epigenetic mark with important regulatory roles in cellular identity and can be quantified at base resolution using bisulfite sequencing. Most studies are limited to the average DNA methylation levels of individual CpGs and thus neglect heterogeneity within the profiled cell populations. To assess this within-sample heterogeneity (WSH) several window-based scores that quantify variability in DNA methylation in sequencing reads have been proposed. We performed the first systematic comparison of four published WSH scores based on simulated and publicly available datasets. Moreover, we propose two new scores and provide guidelines for selecting appropriate scores to address cell-type heterogeneity, cellular contamination and allele-specific methylation. Most of the measures were sensitive in detecting DNA methylation heterogeneity in these scenarios, while we detected differences in susceptibility to technical bias. Using recently published DNA methylation profiles of Ewing ...
In this study we present the first pooled analysis of genome-wide DNA methylation data from HM450K in HNSCCs. Compared with the largest cohort (TCGA) for which HM450K data were available, the pooled cohorts have 43% more HPV(+) cases analysed (63 vs 36), leading to a prevalence of 19% of HPV(+) cases. Moreover, many head and neck organs are included, allowing an assessment of HPV methylation signatures in different anatomic sites. Globally, our results show that HPV has a specific and genome-wide effect in shaping the DNA methylome of HNSCCs that is independent of other known major risk factors, such as tobacco smoking and alcohol consumption. Our results are similar to a recent report based on the analysis of the whole TCGA cohort [29]. The authors identified five subclusters of HNSSC based on DNA methylation patterns (528 samples), four HPV(-) clusters and one HPV(+) cluster [29].. Previous works reported aberrant hypermethylation in gene promoters of HPV(+) oropharyngeal cancer cases [2, 3, ...
TY - JOUR. T1 - Aberrant DNA methylation status in human uterine leiomyoma. AU - Yamagata, Yoshiaki. AU - Maekawa, Ryo. AU - Asada, Hiromi. AU - Taketani, Toshiaki. AU - Tamura, Isao. AU - Tamura, Hiroshi. AU - Ogane, Jun. AU - Hattori, Naka. AU - Shiota, Kunio. AU - Sugino, Norihiro. PY - 2009. Y1 - 2009. N2 - Aberrant DNA methylation has been implicated in tumorigenesis. This study was undertaken to establish the genome-wide DNA methylation profile in uterine leiomyomas and to investigate whether DNA methylation status is altered in uterine leiomyomas. For this purpose, restriction landmark genomic scanning (RLGS) was performed on a paired sample of leiomyoma and adjacent normal myometrium. The RLGS profile revealed 29 aberrant methylation spots (10 methylated and 19 demethylated) in leiomyoma in comparison with myometrium. One of the differently methylated genomic loci was newly identified as GS20656 from the human genome sequence database. In 9 of the 10 paired samples, the DNA methylation ...
Proper propagation of epigenetic information during somatic cell divisions is critical for preserving gene expression patterns and cellular identity. However, the molecular mechanisms responsible for faithful inheritance of epigenetic marks are still poorly understood. In this thesis work, I have studied the inheritance of DNA methylation patterns through somatic divisions, focusing on the role of DNA methyltransferases 3A and 3B in this process.; DNA methylation patterns are established during development and then maintained through multiple somatic cell divisions by co-operative activity of the de novo and maintenance DNA methyltransferases - DNMT3A/3B and DNMT1, respectively. A key question that remains unresolved is how the de novo DNMT3A/3B enzymes assist in faithful inheritance of methylation patterns in somatic cells while guarding against aberrant de novo DNA methylation. Using sucrose density gradient analyses of fractionated chromatin, I have shown that almost all of the cellular ...
Bisulfite sequencing is widely employed to study the role of DNA methylation in disease; however, the data suffer from biases due to coverage depth variability. Imputation of methylation values at low-coverage sites may mitigate these biases while also identifying important genomic features associated with predictive power. Here we describe BoostMe, a method for imputing low-quality DNA methylation estimates within whole-genome bisulfite sequencing (WGBS) data. BoostMe uses a gradient boosting algorithm, XGBoost, and leverages information from multiple samples for prediction. We find that BoostMe outperforms existing algorithms in speed and accuracy when applied to WGBS of human tissues. Furthermore, we show that imputation improves concordance between WGBS and the MethylationEPIC array at low WGBS depth, suggesting improved WGBS accuracy after imputation. Our findings support the use of BoostMe as a preprocessing step for WGBS analysis.
TY - JOUR. T1 - A systematic study of normalization methods for Infinium 450K methylation data using whole-genome bisulfite sequencing data. AU - Wang, Ting. AU - Guan, Weihua. AU - Lin, Jerome. AU - Boutaoui, Nadia. AU - Canino, Glorisa. AU - Luo, Jianhua. AU - Celedón, Juan Carlos. AU - Chen, Wei. N1 - Funding Information: This study was supported by the Competitive Medical Research Fund (WC) from the University of Pittsburgh, and by grants HL07996 and HL117191 (JCC) from the US. National Institutes of Health.. PY - 2015/1/1. Y1 - 2015/1/1. N2 - DNA methylation plays an important role in disease etiology. The Illumina Infinium HumanMethylation450 (450K) BeadChip is a widely used platform in large-scale epidemiologic studies. This platform can efficiently and simultaneously measure methylation levels at ∼480,000 CpG sites in the human genome in multiple study samples. Due to the intrinsic chip design of 2 types of chemistry probes, data normalization or preprocessing is a critical step to ...
This study aimed to assess the effects of PAE on genome-wide DNA methylation patterns and identify an epigenetic signature of FASD, using a large cohort of human subjects. Significant changes to the DNA methylation profiles in BECs of children with FASD compared to age- and sex-matched typically developing controls were identified, with 658 CpGs displaying significantly altered DNA methylation levels, of which 41 had a ,5 % methylation change. Moreover, 101 DMRs containing two or more sequential DM CpGs were identified throughout the genome, spanning 95 different genes, overlapping with several from the initial differential methylation analysis at single CpG level. The majority of DM genes were highly expressed in postmortem brain samples from the Allen Brain Institute. Moreover, BEC and independent cortical samples showed relatively high concordance of DNA methylation levels. As discussed in more detail below, several lines of evidence converge to support the validity of our data. First, a ...
Sequencing-based approaches have led to new insights about DNA methylation. While many different techniques for genome-scale mapping of DNA methylation have been employed, throughput has been a key limitation for most. To further facilitate the mapping of DNA methylation, we describe a protocol for gel-free multiplexed reduced representation bisulfite sequencing (mRRBS) that reduces the workload dramatically and enables processing of 96 or more samples per week. mRRBS achieves similar CpG coverage to the original RRBS protocol, while the higher throughput and lower cost make it better suited for large-scale DNA methylation mapping studies, including cohorts of cancer samples. ...
CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation. Telomerase plays an important role in the development of cellular immortality and oncogenesis. To gain insight into the role of epigenetic aberration of telomerase-related genes in hepatocarcinogenesis, we determined a hypermethylation profile in HCC. We examined the promoter methylation status of 9 genes associated with telomerase activity in 120 HCC, 120 cirrhosis tissues and 10 normal liver tissues by methylation-specific PCR. Assay of telomerase activity was by TRAP-ELISA. The frequency of promoter methylation of each gene was P21 63.3%, P15 42.5%, P16 62.5%, P53 14.2%, RB 32.5%, P27 48.3%, WTI 54.2%, E2F-1 70.8% and P300 65.8% of 120 HCC. Methylation status of P21, P15, P16, WTI and E2F-1 was significantly associated with HCC and nontumor tissues (p | 0.05). CIMP+ was detected in 61.7% (74/120) HCC and 15% (18/120) cirrhosis tissues, no CIMP+ was present in normal liver tissues (p | 0.001).
TY - JOUR. T1 - DNA methylation profiles in type 1 diabetes twins point to strong epigenetic effects on etiology. AU - Stefan, Mihaela. AU - Zhang, Weijia. AU - Concepcion, Erlinda. AU - Yi, Zhengzi. AU - Tomer, Yaron. PY - 2014/5. Y1 - 2014/5. N2 - Type 1 diabetes (T1D) shows ~40% concordance rate in monozygotic twins (MZ) suggesting a role for environmental factors and/or epigenetic modifications in the etiology of the disease. The aim of our study was to dissect the contribution of epigenetic factors, particularly, DNA methylation (DNAm), to the incomplete penetrance of T1D. We performed DNAm profiling in lymphocyte cell lines from 3 monozygotic (MZ) twin pairs discordant for T1D and 6 MZ twin pairs concordant for the disease using HumanMethylation27 BeadChip. This assay assesses the methylation state of 27,578 CpG sites, mostly located within proximal promoter regions. We identified 88 CpG sites displaying significant methylation changes in all T1D-discordant MZ twin pairs. Functional ...
Methylation of CpG island promoters is an epigenetic event that can effectively silence transcription over multiple cell generations. was achieved specifically through Tet3-mediated hydroxymethylation. Collectively our findings reveal a new mechanism that may be exploited to facilitate therapeutic DNA demethylation to reverse kidney fibrosis. In recent years epigenetics have emerged as determinants of fibrosis in the kidney (and other tissues as well).1-5 Furthermore epigenetics have been implied to contribute to the individual susceptibilities of CKD patients to develop fibrosis.1-3 Among the known epigenetic mechanisms methylation of CpG island promoters (referred to as DNA methylation) is the most potent to silence transcription of affected genes.6 Because transcriptional silencing of affected genes has been shown to causally contribute to fibroblast activation and Sapitinib fibrogenesis inhibition or reversal of such aberrant methylation is considered beneficial for the kidney.3 Although in ...
CpG island hypermethylation is an epigenetic control aberration that is important for gene inactivation in cancer cells. Hypermethylation of CpG islands has been described in almost every type of tumor. Many important cellular pathways, such as DNA repair (hMLH1, for example), cell cycle (p14ARF), apoptosis (DAPK), cell adherence (CDH1, CDH13), are inactivated by this epigenetic lesion. Hypermethylation is linked to methyl-binding proteins, DNA methyltransferases and histone deacetylase, but the degree to which this process selectively silences tumor suppressor genes continues to remain a vibrant field of study. The list for hypermethylated genes is growing and functional and genetic studies are being performed to determine which hypermethylation events are relevant for tumorigenesis. Basic as well as translational research will be needed to understand the mechanisms and roles of CpG island hypermethylation in cancer. The first discovery of methylation in a CpG island of a tumor suppressor gene ...
Restriction landmark genomic scanning (RLGS) has been used to study aberrant CpG island methylation in cancer for more than ten years. This approach remains one of the most reliable ways to characterize CpG island hypermethylation in cancer and has been used both to characterize differences in aberrant methylation phenotypes and also to identify tumor suppressor genes. Not only have known tumor suppressor genes like Cdkn2a (p16), Itga4 (α 4-integrin) [1], and Igfbp7 [2] been identified as targets of aberrant methylation in cancer by RLGS, but also novel tumor suppressor genes such as TCF21 [3], SLC5A8 [4], ID4 [5], BMP3B [6], and SOCS1 [7] have been identified by RLGS.. RLGS is a two-dimensional gel electrophoresis method [8] that allows detection of DNA methylation if a methylation sensitive landmark enzyme such as NotI is used. Up to 2,000 end-labeled landmark sites are displayed in a single RLGS profile. The labeling of the sites is based on incorporation of radionucleotides into the NotI ...
Southern analysis has shown that DNA from 25% of primary estrogen receptor (ER) α-negative breast tumors displays aberrant methylation at one site within the ER gene CpG island. To examine more sites and increase sensitivity, we developed a methylation-specific PCR assay to map methylation of the entire ER CpG island. The island was unmethylated in normal breast tissue and ER-positive breast cancer cell lines, but extensively methylated in all ER-negative cell lines and breast tumors examined. In addition, some of the ER-positive/progesterone receptor-negative and ER-positive/progesterone receptor-positive tumors (about 70% and 35%, respectively) displayed methylation of the ER CpG island, suggesting that this heterogeneity within tumor cell populations could potentially shed light on the etiology of ER-negative recurrent tumors arising from ER-positive tumors.. ...
Stress and antidepressant treatment can modulate DNA methylation in promoter region of genes related to neuroplasticity and mood regulation, thus implicating this epigenetic mechanism in depression neurobiology and treatment. Accordingly, systemic administration of DNA methyltransferase (DNMT) inhibitors induces antidepressant-like effects in rodents. DNA methylation is conveyed by DNMT 1, 3a and 3b isoforms, which are differentially expressed in the brain. In order to investigate if the behavioral effects of antidepressants could be associated with changes in DNA methylation and DNMT expression, we investigated the effects induced by acute and repeated antidepressant treatment on DNA methylation and DNMT expression (1, 3a and 3b isoforms) in different brain regions of rats exposed to a stress model of depression, the learned helplessness (LH). Therefore, rats were exposed to pretest and treated with one or seven injections of vehicle or imipramine (15, with test session performed one ...
TY - JOUR. T1 - Epigenetic regulation of multidrug resistance 1 gene expression. T2 - profiling CpG methylation status using bisulphite sequencing.. AU - Baker, Emma K. AU - El-Osta, Assam. PY - 2010. Y1 - 2010. N2 - Methylation of CpG dinucleotides is one of the major epigenetic processes involved in the regulation of gene expression. Catalyzed by DNA methyltransferases, hypermethylation of CpG islands in promoter regions is typically associated with gene silencing. DNA methylation plays an important role in normal differentiation, development, and maintenance of genomic stability, with aberrant CpG methylation being linked with a number of disease states. Three CpG islands within a 1.15- kb region characterize the chromatin landscape surrounding the transcriptional start site of the multidrug resistance 1 (MDR1) gene. We and others have demonstrated that hypermethylation of this region is correlated with MDR1 gene silencing and the inability of chemotherapeutic agents to activate MDR1 ...
TY - JOUR. T1 - Epigenetic variation in monozygotic twins. T2 - A genome-wide analysis of DNA methylation in buccal cells. AU - van Dongen, Jenny. AU - Ehli, Erik A.. AU - Slieker, Roderick C.. AU - Bartels, Meike. AU - Weber, Zachary M.. AU - Davies, Gareth E.. AU - Slagboom, P. Eline. AU - Heijmans, Bastiaan T.. AU - Boomsma, Dorret I.. PY - 2014/1/1. Y1 - 2014/1/1. N2 - DNA methylation is one of the most extensively studied epigenetic marks in humans. Yet, it is largely unknown what causes variation in DNA methylation between individuals. The comparison of DNA methylation profiles of monozygotic (MZ) twins offers a unique experimental design to examine the extent to which such variation is related to individual-specific environmental influences and stochastic events or to familial factors (DNA sequence and shared environment). We measured genome-wide DNA methylation in buccal samples from ten MZ pairs (age 8-19) using the Illumina 450k array and examined twin correlations for methylation ...
Alterations in the methylation patterns of promoter CpG islands have been associated with the transcriptional inhibition of genes in many human cancers. These epigenetic alterations could be used as molecular markers for the early detection of cancer-that is, while potentially curable according to current therapeutic strategies. In prostate cancer, GSTP1 hypermethylation is the most common epigenetic alteration, and can be detected in up to 90% of cases. Thus, screening for methylation of other loci would probably increase the number of primary tumours amenable to screening. Moreover, previous studies have shown that the endothelin B receptor (EDNRB) gene is abnormally methylated in a high proportion of prostate tumours ( approximately 70%).. To investigate the potential use of EDNRB gene hypermethylation as a prostate cancer specific marker.. Methylation specific polymerase chain reaction (MSP) for the promoter region of EDNRB was performed on prospectively collected tissue samples from 48 ...
Imprinted genes are expressed predominantly from either their paternal or their maternal allele. To date, all imprinted genes identified in plants are expressed in the endosperm. In Arabidopsis thaliana, maternal imprinting has been clearly demonstrated for the Polycomb group gene MEDEA (MEA) and for FWA. Direct repeats upstream of FWA are subject to DNA methylation. However, it is still not clear to what extent similar cis-acting elements may be part of a conserved molecular mechanism controlling maternally imprinted genes. In this work, we show that the Polycomb group gene FERTILIZATION-INDEPENDENT SEED2 (FIS2) is imprinted. Maintenance of FIS2 imprinting depends on DNA methylation, whereas loss of DNA methylation does not affect MEA imprinting. DNA methylation targets a small region upstream of FIS2 distinct from the target of DNA methylation associated with FWA. We show that FWA and FIS2 imprinting requires the maintenance of DNA methylation throughout the plant life cycle, including male ...
Background: The risk of developing Barretts esophagus (BE) and/or esophageal adenocarcinoma (EAC) is associated with specific demographic and behavioral factors, including gender, obesity/elevated body-mass index (BMI), and tobacco use. Alterations in DNA methylation, an epigenetic modification that can affect gene expression and that can be influenced by environmental factors, is frequently present in both BE and EAC and is believed to play a role in the formation of BE and its progression to EAC. It is currently unknown whether obesity or tobacco smoking influence the risk of developing BE/EAC via the induction of alterations in DNA methylation. To investigate this possibility, we assessed the genome-wide methylation status of 81 esophageal tissues, including BE, dysplastic BE, and EAC epithelia using HumanMethylation450 BeadChips (Illumina). Results: We found numerous differentially methylated loci in the esophagus tissues when comparing males to females, obese to lean individuals, and smokers to
Cytosine DNA methylation is a heritable process which plays important roles in regulating development throughout the life cycle of an organism. Although methylation of nuclear DNA has been studied extensively, little is known about the state and role of DNA methylation in chloroplast genomes, especially in marine algae. Here, we have applied an integrated approach encompassing whole-genome bisulfite sequencing, methylated DNA immunoprecipitation, gene co-expression networks and photophysiological analyses to provide evidence for the role of chloroplast DNA methylation in a marine alga, the multicellular brown alga Saccharina japonica. Although the overall methylation level was relatively low in the chloroplast genome of S. japonica, gametophytes exhibited higher methylation levels than sporophytes. Gene-specific bisulfite-cloning sequencing provided additional evidence for the methylation of key photosynthetic genes. Many of them were highly expressed in sporophytes whereas genes involved in ...
We have recently identified HOP hoemobox (HOPX) as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers, and it can remarkably inhibit tumors aggressive phenotypes. In this current study, we for the first time examined methylation level of HOPX and tested the functional relevance in pancreatic cancer (PC). Clinical features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and immunohistochemistry was added. We also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis. PC tissues had HOPX gene hypermethylation as compared to the corresponding normal pancreas tissues, and its uniqueness was robust to discriminate tumor from normal tissues (AUC = 0.85, P | 0.0001). Unexpectedly, HOPX was increased in expression in tumor tissues, and immunohistochemistry revealed its predominant expression in the Langerhans islet cells, where HOPX was reduced in expression
We identified differential methylation by tumor histology in a series of pediatric GCTs, with evidence that YSTs exhibit promoter hypermethylation in a large number of cancer-related genes while germinomas and teratomas do not. These CpG loci were not hypermethylated in the normal adjacent tissue from two patients with YSTs, suggesting that methylation patterns also distinguish yolk sac tumor tissue from normal ovary or testis tissue. Four pathways, most notably a human embryonic stem cell pathway, were over-represented among the CpG loci that were hypermethylated in YSTs. A smaller number of CpG loci exhibited significantly different methylation in a comparison of mature and immature teratomas, however these loci were strikingly enriched for genes associated with embryonic stem cell pluripotency and developmental signaling pathways, such as PTEN, PDGF and NF-κB. In addition, immature teratomas were enriched for differential methylation of genes involved in axonal guidance signaling, reflecting ...
Background: Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers. Methods: The quantitative methylation analysis was performed using the SEQUENOMs EpiTYPER (TM) assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results: The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for ...
TY - JOUR. T1 - Specific 5′CpG island methylation signatures of FHIT and p16 genes and their potential diagnostic relevance in Indian breast cancer patients. AU - Naqvi, Raza A. AU - Hussain, Arif. AU - Raish, Mohmammad. AU - Noor, Afshan. AU - Shahid, Mohammad. AU - Sarin, Ritu. AU - Kukreti, Himani. AU - Khan, Nida Jameel. AU - Ahmad, Shandar. AU - Deo, Suryanarayan V.S.. AU - Husain, Syed Akhtar. AU - Pasha, Syed Tazeen. AU - Basir, Seemi Farhat. AU - Shukla, Nootan Kumar. PY - 2008/9/1. Y1 - 2008/9/1. N2 - Even after tremendous molecular studies, early detection, more accurate and sensitive diagnosis, and prognosis of breast cancer appear to be a riddle so far. To stab the enigma, this study is designed to envisage DNA methylation signatures as cancer-specific and stage-specific biomarkers in Indian patients. Rigorous review of scattered scientific reports on aberrant DNA methylation helped us to select and analyze a potential tumor suppressor gene pair (FHIT and p16 genes) in breast ...
The human CGGBP1 binds to GC-rich regions and interspersed repeats, maintains homeostasis of stochastic cytosine methylation and determines DNA-binding of CTCF. Interdependence between regulation of cytosine methylation and CTCF occupancy by CGGBP1 remains unknown. By analyzing methylated DNA-sequencing data obtained from CGGBP1-depleted cells, we report that some transcription factor-binding sites, including CTCF, resist stochastic changes in cytosine methylation. By analysing CTCF-binding sites we show that cytosine methylation changes at CTCF motifs caused by CGGBP1 depletion resist stochastic changes. These CTCF-binding sites are positioned at locations where the spread of cytosine methylation in cis depends on the levels of CGGBP1. Our findings suggest that CTCF occupancy and functions are determined by CGGBP1-regulated cytosine methylation patterns.
We performed a comparative analysis of the genome-wide DNA methylation profiles from three human embryonic stem cell (HESC) lines. It had previously been shown that HESC lines had significantly higher non-CG methylation than differentiated cells, and we therefore asked whether these sites were conserved across cell lines. We find that heavily methylated non-CG sites are strongly conserved, especially when found within the motif TACAG. They are enriched in splice sites and are more methylated than other non-CG sites in genes. We next studied the relationship between allele-specific expression and allele-specific methylation. By combining bisulfite sequencing and whole transcriptome shotgun sequencing (RNA-seq) data we identified 1,020 genes that show allele-specific expression, and 14% of CG sites genome-wide have allele-specific methylation. Finally, we asked whether the methylation state of transcription factor binding sites affects the binding of transcription factors. We identified variations in
TY - JOUR. T1 - Promoter hypermethylation of CIDEA, HAAO and RXFP3 associated with microsatellite instability in endometrial carcinomas. AU - Huang, Yi Wen. AU - Luo, Jingqin. AU - Weng, Yu I.. AU - Mutch, David G.. AU - Goodfellow, Paul J.. AU - Miller, David S.. AU - Huang, Tim H.M.. N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.. PY - 2010/5. Y1 - 2010/5. N2 - Objective: DNA promoter methylation is an epigenetic phenomenon for long-term gene silencing during tumorigenesis. The purpose of this study is to identify novel hypermethylated loci associated with clinicopathologic variables in endometrioid endometrial carcinomas. Methods: To find hypermethylated promoter loci, we used differential methylation hybridization coupling with microarray and further validated by combined bisulfite restriction analysis and MassARRAY assay. Methylation levels of candidate loci were corrected with clinicopathologic factors of endometrial carcinomas. Results: Increased promoter methylation ...
Barretts esophagus is a premalignant condition of the distal esophagus that increases the risk of esophageal cancer. Unfortunately, screening for Barretts esophagus currently requires endoscopy, an invasive and expensive procedure, and thus, it is not routinely performed. Moinova et al. have now demonstrated a simplified approach to screening by identifying a pair of DNA methylation markers that correlate with the presence of Barretts esophagus. The authors also invented a swallowable balloon-based device that can capture DNA samples for methylation analysis and found that it is well tolerated in patients and provides ,90% sensitivity and specificity compared to endoscopy, suggesting its potential as a screening method. ...
The purpose of this workshop is to get a deeper understanding of the use of bisulfite-treated DNA in order to analyze the epigenetic layer of DNA methylation. Advantages and disadvantages of the so-called bisulfite sequencing and its implications on data analyses will be covered. The participants will be trained to understand bisulfite-treated NGS data, to detect potential problems/errors and finally to implement their own pipelines. After this course they will be able to analyze DNA methylation and create ready-to-publish graphics.. By the end of this workshop the participants will:. be familiar with the sequencing method of ...
In recent years, great progress has been achieved towards identifying novel biomarkers in lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), at the genomic, transcriptomic and epigenomic level for accurate risk-stratification and prediction of treatment response. In paper I, we validated the prognostic relevance of a recently proposed RNA-based marker in CLL, UGT2B17, and analyzed its expression levels in 253 early-stage patients. Besides confirming its prognostic impact in multivariate analysis, we could identify 30% of IGHV-mutated CLL (M-CLL) cases with high expression and poor outcome, which otherwise lacked any other poor-prognostic marker. In paper II, we investigated the prognostic impact of a previously reported 5 CpG signature that divides CLL patients into three clinico-biological subgroups, namely naive B-cell-like CLL (n-CLL), memory B-cell-like CLL (m-CLL) and intermediate CLL (i-CLL), in 135 CLL patients using pyrosequencing. We ...
Inactivaion of tumor suppressor genes (TSGs) by promoter CpG methylation frequently occurs in tumorigenesis, even in the early stages, contributing to the initiation and progression of human cancers. Deleted in lung and esophageal cancer 1 (DLEC1), located at the 3p22-21.3 TSG cluster, has been identified frequently silenced by promoter CpG methylation in multiple carcinomas, however, no study has been performed for lymphomas yet. We examined the expression of DLEC1 by semi-quantitative reverse transcription (RT)-PCR, and evaluated the promoter methylation of DLEC1 by methylation-specific PCR (MSP) and bisulfite genomic sequencing (BGS) in common lymphoma cell lines and tumors. Here we report that DLEC1 is readily expressed in normal lymphoid tissues including lymph nodes and PBMCs, but reduced or silenced in 70% (16/23) of non-Hodgkin and Hodgkin lymphoma cell lines, including 2/6 diffuse large B-cell (DLBCL), 1/2 peripheral T cell lymphomas, 5/5 Burkitt, 6/7 Hodgkin and 2/3 nasal killer (NK)/T-cell
Enhanced Reduced Representation Bisulfite Sequencing is a method for the preparation of sequencing libraries for DNA methylation...
Genomic imprinting is exclusive to mammals and seed plants and refers to parent-of-origin-dependent, differential transcription. As previously shown in mammals, studies in Arabidopsis have implicated DNA methylation as an important hallmark of imprinting. The current model suggests that maternally expressed imprinted genes, such as MEDEA (MEA), are activated by the DNA glycosylase DEMETER (DME), which removes DNA methylation established by the DNA methyltransferase MET1. We report the systematic functional dissection of the MEA cis-regulatory region, resulting in the identification of a 200-bp fragment that is necessary and sufficient to mediate MEA activation and imprinted expression, thus containing the imprinting control region (ICR). Notably, imprinted MEA expression mediated by this ICR is independent of DME and MET1, consistent with the lack of any significant DNA methylation in this region. This is the first example of an ICR without differential DNA methylation, suggesting that factors ...
The maintenance methyltransferase Dnmt1 and the de novo methyltransferase Dnmt3b cooperate to maintain DNA methylation and genomic stability in the adult intestinal epithelium.
© 2019 The Author(s) 2019. Published by Oxford University Press. Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using
Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type 2 diabetes, cardiovascular disease and related metabolic and inflammatory disturbances. Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation, a key regulator of gene expression and molecular phenotype. Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P , 1 × 10 -7, range P = 9.2 × 10 -8 to 6.0 × 10 -46; n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P , 0.05), and show that sentinel methylation markers identify gene ...
Precise mapping of DNA methylation patterns in CpG islands has become essential for understanding diverse biological processes such as the regulation of imprinted genes, X chromosome inactivation, and tumor suppressor gene silencing in human cancer. We describe a new method, MSP (methylation-specific PCR), which can rapidly assess the methylation status of virtually any group of CpG sites within a CpG island, independent of the use of methylation-sensitive restriction enzymes. This assay entails initial modification of DNA by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequent amplification with primers specific for methylated versus unmethylated DNA. MSP requires only small quantities of DNA, is sensitive to 0.1% methylated alleles of a given CpG island locus, and can be performed on DNA extracted from paraffin-embedded samples. MSP eliminates the false positive results inherent to previous PCR-based approaches which relied on differential ...
To cast light on the contribution of methylation to genesis of ulcerative colitis (UC)-associated tumors, promoter methylation and expression of O6-methylguanine DNA methyltransferase (MGMT), hMLH1, p16INK4, and E-cadherin were examined in 14 low-grade dysplasias (LGDs), 15 high-grade dysplasias (HGDs), and 14 adenocarcinomas associated with UC and, for comparison, in 30 sporadic adenomas with LGD, 30 adenomas with HGD, and 60 adenocarcinomas, using methylation-specific polymerase chain reaction and immunohistochemical analysis. The frequency of MGMT and hMLH1 methylation in UC-associated tumors was low, with a significant difference between HGD and sporadic adenomas with HGD of the left hemicolon. The methylation frequency of p16INK4 in UC-associated tumors was also relatively low compared with sporadic colonic tumors. For E-cadherin, methylation was limited in both types of tumor. Decrease of expression of MGMT, hMLH1, and p16INK4 was significantly correlated with methylation. Thus, compared ...
... consequences of aberrant DNA methylation in complex chronic diseases, existing modulators of DNA methylation used in the clinic ... Junk DNA: A Journey Through the Dark Matter of the Genome, examines developments in the study of junk DNA, or noncoding DNA. ... ISBN 978-1-84973-882-8. Heightman, Tom D.; McCullar, Michael (20 November 2015). "CHAPTER 4. Targeting DNA Methylation". In ... From Ernest Hemingway's mutant cat to exoneration of the innocent through DNA fingerprinting, junk DNA impacts on an ...
Law's pioneering work on DNA methylation patterns led to the discovery of the role of the CLASSY protein family in DNA ... Dynamic DNA methylation. (2009) Science. 323(5921):1568-9. DOI: 10.1126/science.1172782 Johnson, L.M., Law, J.A., Khattar, A., ... DOI: 10.1073/pnas.1810582115 Zhou, M., Palanca, A.M.S., Law, J.A. Locus-specific control of the de novo DNA methylation pathway ... Law's postdoctoral work, studying DNA methylation at UC Los Angeles, was followed by her recruitment for a faculty position at ...
Enzymatic DNA Methylation. Springer Science & Business Media. 7 March 2013. pp. 3-. ISBN 978-3-642-74734-2.. ...
... the role of DNA methylation in normal plant development. DNA methylation is a biochemical process that modifies DNA, with ... and her work demonstrating that DNA methylation (a biochemical process that modifies the plant's DNA) is essential for normal ... Finnegan, E. J.; Genger, R. K.; Peacock, W. J.; Dennis, E. S. (1998). "DNA Methylation in Plants". Annual Review of Plant ... Finnegan, E J; Peacock, W J; Dennis, E S (2000). "DNA methylation, a key regulator of plant development and other processes". ...
DNA methylation is a process by which methyl groups attach to DNA structure causing the gene to not be expressed. This is ... Edwards JR, Yarychkivska O, Boulard M, Bestor TH (2017-05-08). "DNA methylation and DNA methyltransferases". Epigenetics & ... where they seem to inhibit these methylation patterns with some success at reducing symptoms. The DNA methylation inhibitor ... The first is DNA methylation, where a cytosine residue that is followed by a guanine residue (CpG) is methylated. In general, ...
DNA Methylation and Gene Regulation. Holliday, R., M. Monk and J.E. Pugh (eds). The Royal Society, London (1990). Proceedings ... The main focus of his experimental work was the epigenetic control of gene expression by DNA methylation in CHO cells. These ... In 1975 he suggested that DNA methylation could be an important mechanism for the control of gene expression in higher ... Experimental Gerontology 37, 851-857 (2002) Early studies on recombination and DNA repair in Ustilago maydis. DNA Repair, 3, ...
Variations in DNA methylation of normal cells compared to malignant cells shows a prominent mechanism in how cancerous cells ... The silencing of genes created by abnormal DNA methylation is a major contributor to the formation of cancerous tumors. ... A leading therapeutic strategy in treating solid tumors stems from the use of demethylating agents to suppress DNA methylation ... As more research is completed in the field of genetic mutations, specifically involving DNA Methylation, these drugs can be ...
Han L, Witmer PD, Casey E, Valle D, Sukumar S (August 2007). "DNA methylation regulates MicroRNA expression". Cancer Biology & ... This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene ... Kim J, Bhinge AA, Morgan XC, Iyer VR (January 2005). "Mapping DNA-protein interactions in large genomes by sequence tag ... "The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors". Nucleic Acids ...
Edwards, John R.; Yarychkivska, Olya; Boulard, Mathieu; Bestor, Timothy H. (2017). "DNA methylation and DNA methyltransferases ... 2017). "Impact of cytosine methylation on DNA binding specificities of human transcription factors". Science. 356 (6337): ... such as histone modification and DNA methylation). Giving an analogy of his mother and her twin sister, he explains: Chance ... It is now generally believed that histone modification and DNA methylations are major factors of epigenetic functions, aging ...
Chromatin structure and DNA damage repair (Dinant et al., 2008) Profiling genome-wide DNA methylation (Yong et al., 2016) ... Yong, Wai-Shin; Hsu, Fei-Man; Chen, Pao-Yang (2016-06-29). "Profiling genome-wide DNA methylation". Epigenetics & Chromatin. 9 ... Dinant, Christoffel; Houtsmuller, Adriaan B.; Vermeulen, Wim (2008-11-12). "Chromatin structure and DNA damage repair". ...
DNA cytosine methylation is catalyzed by DNA methyltransferases (DNMTs). Methylcytosine demethylation is catalyzed in several ... Wang Z, Tang B, He Y, Jin P (March 2016). "DNA methylation dynamics in neurogenesis". Epigenomics. 8 (3): 401-14. doi:10.2217/ ... Epigenetic modifications include DNA cytosine methylation to form 5-methylcytosine and 5-methylcytosine demethylation. These ... At different stages of mammalian nervous system development two DNA repair processes are employed in the repair of DNA double- ...
DNA cytosine methylation is catalyzed by DNA methyltransferases (DNMTs). Methylcytosine demethylation is catalyzed in several ... Epigenetic modifications include DNA cytosine methylation to form 5-methylcytosine and 5-methylcytosine demethylation. These ... Wang, Zhiqin; Tang, Beisha; He, Yuquan; Jin, Peng (2016). "DNA methylation dynamics in neurogenesis". Epigenomics. 8 (3): 401- ... "Assessment and site-specific manipulation of DNA (Hydroxy-)methylation during mouse corticogenesis". Life Science Alliance. 2 ( ...
It was from this compound that DNA methylation was discovered as it was the first molecule found to contain 5-methylcytosine. ... Neumann HP (2008). Progress in DNA Methylation Research. Nova. p. 190. ISBN 1600217222. History of discovery at Internet ... In 1948, Hotchkiss separated the nucleic acids of DNA from calf thymus using paper chromatography, by which he detected a ...
DNMT1 is the enzyme involved in the maintenance of DNA methylation marks. DNMT1 is recruited to DNA during its replication, or ... DNMT3b is thought to be critical to de novo methylation, or the production of new methylation marks on DNA. This increased ... Chemicals in smoke can damage DNA, which subsequently leads to changes in DNA methylation during the repair process. Damage ... This down-regulation of DNMT1 can have serious consequences on DNA methylation, namely a failure to maintain normal methylation ...
Li, Long-Cheng; Okino, Steven T.; Dahiya, Rajvir (2004-09-20). "DNA methylation in prostate cancer". Biochimica Et Biophysica ...
DNA methylation turns a gene "off" - it results in the inability of genetic information to be read from DNA; removing the ... proteins around which DNA is wrapped) and DNA methylation. These epigenetic changes can influence the growth of neurons in the ... Epigenetic differences in DNA methylation of the CpG islands proximal to the DLX1 gene correlated with the differing behavior. ... Even short-term substance abuse can produce long-lasting epigenetic changes in the brain of rodents, via DNA methylation and ...
"It could have been anyone's DNA, but as a pioneer in DNA methylation epigenetics, there is something special to me about it ... and examine the protein-DNA binding of the crystals using high-resolution DNA methylation analysis. They were able to clone ... DNA methylation is believed to pass information from parent cells to daughter cells, functioning as a secondary, high-fidelity ... Through ongoing research he has helped to understand the mechanisms of DNA methylation and gene regulation. In the 1980s, Riggs ...
January 2016). "DNA methylation changes in plasticity genes accompany the formation and maintenance of memory". Nature ... In mammalian nuclear DNA, a methyl group can be added, by a DNA methyltransferase, to the 5th carbon of cytosine to form 5mC ( ... The DNA damage 8-OHdG is a product of ROS interaction with DNA. Numerous studies have shown that 8-OHdG increases in different ... Day JJ, Sweatt JD (November 2010). "DNA methylation and memory formation". Nature Neuroscience. 13 (11): 1319-23. doi:10.1038/ ...
Han L, Witmer PD, Casey E, Valle D, Sukumar S (Aug 2007). "DNA methylation regulates MicroRNA expression". Cancer Biology & ... This gene is a member of the Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in ... Shanmugam K, Green NC, Rambaldi I, Saragovi HU, Featherstone MS (Nov 1999). "PBX and MEIS as non-DNA-binding partners in ...
Epigenetic modifications include DNA cytosine methylation and post-translational modifications to histones. These mechanisms ... Klose, R.J. & Bird, A.P. (2006). "Genomic DNA methylation: the mark and its mediators". Trends in Biochemical Sciences. 31 (2 ... Kriaucionis, S. & Bird, A. (2003). "DNA methylation and Rett syndrome". Human Molecular Genetics. 12 (2): R221-R227. doi: ... CNVs are the most common type of structural variation in the genome, consisting of deletions and duplications of DNA that range ...
DNA cytosine methylation is catalyzed by DNA methyltransferases (DNMTs). Methylcytosine demethylation is catalyzed in several ... Wang, Z; Tang, B; He, Y; Jin, P (Mar 2016). "DNA methylation dynamics in neurogenesis". Epigenomics. 8 (3): 401-14. doi:10.2217 ... Key epigenetic modifications include DNA cytosine methylation to form 5-methylcytosine and 5-methylcytosine demethylation. ... "Assessment and site-specific manipulation of DNA (hydroxy-)methylation during mouse corticogenesis". Life Sci Alliance. 2 (2): ...
Han L, Witmer PD, Casey E, Valle D, Sukumar S (August 2007). "DNA methylation regulates MicroRNA expression". Cancer Biology & ...
... a large proportion of carcinogenic gene silencing is a result of altered DNA methylation (see DNA methylation in cancer). DNA ... In humans, DNA methylation occurs at the 5' position of the pyrimidine ring of the cytosine residues within CpG sites to form 5 ... Silencing of DNA repair genes through methylation of CpG islands in their promoters appears to be especially important in ... Bird A (2002). "DNA methylation patterns and epigenetic memory". Genes Dev. 16 (1): 6-21. doi:10.1101/gad.947102. PMID 11782440 ...
Riggs, A.D. (1975). "X inactivation, differentiation, and DNA methylation". Cytogenet Cell Genet. 14: 9-25. doi:10.1159/ ...
Dec 1999). DNA Methylation, Stem Cells and Cancer. Rickert CH, Paulus W (Jan 2001). "Tumors of the choroid plexus". Microscopy ...
The DNA methylation pattern in queens and workers, and between nurses and foragers is different. DNA methylation also increases ... The function of the DNA methylation in honey bees is to regulate gene alternative splicing DNA methylation plays a major role ... But unlike mammals they possess two DNA methyltransferases 1 and just one DNA methyltransferase 3. DNA methylation ... DNA methylation is an epigenetic mechanism. It is a chemical modification of the DNA where a methyl group is attached to ...
The mono-methylation denotes the methylation present in H3K4me1. The genomic DNA of eukaryotic cells is wrapped around special ... H3K4me1 is an epigenetic modification to the DNA packaging protein Histone H3. It is a mark that indicates the mono-methylation ... Neidhart, Michel (2015-09-17). DNA Methylation and Complex Human Disease. p. 124. ISBN 978-0-12-420194-1. "Whole-Genome ... It results in good optimization and is used in vivo to reveal DNA-protein binding occurring in cells. ChIP-Seq can be used to ...
DNA methylation is the covalent addition of a methyl group to a segment of the DNA code. These -CH3 groups are added to ... DNA methylation is one of the most well studied epigenetic mechanisms and there have been several findings linking it to ... Methylation of BDNF DNA has also been shown to be affected by post-natal social experiences, stressful environment, and social ... DNA methylation can also affect expression of BDNF (brain derived neurotrophic factor). The BDNF protein is important for ...
... is a database of methylation data derived from next-generation sequencing data. DNA methylation MethBase MethDB ... a database for next-generation sequencing single-cytosine-resolution DNA methylation data". Nucleic Acids Res. England. 39 ( ...
DNA methylation is reliably inherited through the action of maintenance methylases that modify the nascent DNA strand generated ... For every DNA base pair separated by the advancing polymerase, one hybrid RNA:DNA base pair is immediately formed. DNA strands ... Transcription can be silenced by histone modification (deacetylation and methylation), RNA interference, and/or DNA methylation ... In mammalian cells, DNA methylation is the primary marker of transcriptionally silenced regions. Specialized proteins can ...
... with one proposed mechanism being that of DNA methylation.[30] The intestinal bacteria Prevotella copri and Bacteroides ...
DNA construct. *DNA damage theory of ageing. *DNA methylation. *DNA polymerase. *DNA repair ... Pages in category "DNA". The following 33 pages are in this category, out of 33 total. ... Retrieved from "" ...
"Bdnf DNA methylation modifications in the hippocampus and amygdala of male and female rats exposed to different caregiving ... Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response ... to video stimuli of mother-infant separation as being associated with decreased glucocorticoid receptor gene methylation in the ...
DNA repair. • response to X-ray. • response to drug. • DNA unwinding involved in DNA replication. • cellular response to ... Methylation of the promoter of miR-34a, resulting in under-expression of miR-34a, is observed in 79% of prostate cancers and 63 ... DNA binding. • DNA-dependent ATPase activity. • recombinase activity. • chromatin binding. • DNA polymerase binding. • protein ... DNA synthesis involved in DNA repair. • interstrand cross-link repair. • response to glucoside. • DNA recombinase assembly. • ...
Four phenylalanine residues(Phe57, Phe74, Phe148, Phe 165) on TBP bind to DNA and form kinks in the DNA, forcing the DNA minor ... Histone methylation/Histone methyltransferase *EZH2. *Histone demethylase. *Histone acetylation and deacetylation *Histone ... Compounds that trap the protein-DNA intermediate could result in it being toxic to the cell once they encounter a DNA ... which distorts DNA to allow access of DNA-binding proteins in the minor groove.[45] This will destabilize the interaction ...
Arginine methylation[edit]. What was said above of the chemistry of lysine methylation also applies to arginine methylation, ... DNA damage[edit]. Marking sites of DNA damage is an important function for histone modifications. It also protects DNA from ... di-methylation repression[45] repression[45] activation[44] tri-methylation activation[46] repression[43] repression[43] ... Compacting DNA strands[edit]. Histones act as spools around which DNA winds. This enables the compaction necessary to fit the ...
The accumulation of epigenetic factors, primarily DNA methylation, in the extended LCT region, including the gene enhancer ... The downregulation of lactase expression in mice could be attributed to the accumulation of DNA methylation in the Lct gene and ... Age-dependent expression of LCT in mice intestinal epithelium has been DNA methylation in the gene enhancer.[26] ... The specific DNA sequence in the MCM6 gene helps control whether the LCT gene is turned on or off.[19] At least several ...
See also: Epigenetics of schizophrenia § Methylation of BDNF. A plethora of recent evidence suggests the linkage between ... evaluation of brain-derived neurotrophic factor genomic DNA sequence variation". American Journal of Medical Genetics. 107 (4 ...
The zebrafish has transparent embryos that can be injected with DNA or RNA and has a lifespan of up to two years.[79] Induced ... As of 2013[update] it appeared that differences in the methylation of arginine residues in FUS protein may be relevant, and ... methylation status may be a way to distinguish some forms of FTD from ALS.[146] ...
... that attack and destroy specific regions of the viral DNA of invading bacteriophages. Methylation of the host's own DNA marks ...
Mono-methylation was conducted followed by a reaction with ethyl propiolate in the presence of ZnCl2 to yield 7-hydroxy-5- ... A particular study found that a tan gained with bergapten had less DNA damage in human subjects.[10] Bergapten has been shown ...
In mammals, methylation occurs on DNA and histone proteins. DNA methylation occurs on the cytosine of CpG dinucleotides in the ... DNA methylation. In Alzheimer's disease cases, global DNA hypomethylation and gene-specific hypermethylation has been observed ... but lower levels of methylation in patients greater than 70 years old.[71] Studies on differential DNA methylation in human AD ... DNA-methylation inhibitor chemical analogue of cytidine Azathioprine M (ny) M (ny) ...
Neidhart, M (2016). DNA Methylation and Complex Human Disease (1st ed.). San Diego: Academic Press. p. 22.. ISBN 978-0124201941 ... Neidhart, M (2016). DNA Methylation and Complex Human Disease (1st ed.). San Diego: Academic Press. p. 222.. ISBN 9780124201941 ... regulation of transcription, DNA-templated. • ossification. • platelet degranulation. • multicellular organism development. • ... The mechanism in which CTCF binds to these regions is currently unknown, but could include either a direct DNA-CTCF interaction ...
Bacteria also use DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine ... By preferentially modifying hemimethylated DNA, DNMT1 transfers patterns of methylation to a newly synthesized strand after DNA ... However, bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions ... heritable DNA methylation mutations are 100.000 times more likely to occur compared to DNA mutations.[105] An epigenetically ...
DNA methylation, and imprinted expression of the human SNRPN gene". Am. J. Hum. Genet. 58 (2): 335-46. PMC 1914536. PMID ... different DNA methylation patterns in the Prader-Willi/Angelman syndrome region as determined by the genomic sequencing method ... SNRPN-methylation is used to detect uniparental disomy of chromosome 15.[6] After fluorescent-in-situ-hybridization has ... White HE, Durston VJ, Harvey JF, Cross NC (2006). "Quantitative analysis of SNRPN(correction of SRNPN) gene methylation by ...
"Promoter Methylation Pattern Controls Corticotropin Releasing Hormone Gene Activity in Human Trophoblasts. ". PLoS One. 2017. ... Segment o DNA yw'r genyn, sy'n amgodio ffwythiant arbennig. Mae'r genyn yma wedi ei leoli ar yr edefyn ôl o gromosom dynol 8, ...
DNA repairEdit. The methylation of histone lysine has an important role in choosing the pathway for repairing DNA double-strand ... Wei S, Li C, Yin Z, Wen J, Meng H, Xue L, Wang J (2018). "Histone methylation in DNA repair and clinical practice: new findings ... These epigenetic changes include loss or gain of methylations in both DNA and histone proteins.[18] ... depending on the site of methylation. For example, it is likely that the methylation of lysine 9 on histone H3 (H3K9me3) in the ...
Experimental alteration of DNA methylation affects the phenotypic plasticity of ecologically relevant traits in Arabidopsis ... DNA biopolimero luze bat da, lau base mota ezberdinekin. DNA molekula batean zehar dauden baseen sekuentziak informazio ... DNA sekuentziak kromosoma batean duen kokapen zehatzari locus izena ematen zaio. Locus batean dagoen DNA sekuentzia ezberdina ... From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design. Second Edition. Blackwell Publishing. Oxford. ...
DNA methylation analysis is used to diagnose certain genetic disorders that are caused by disruptions of epigenetic mechanisms ... DNA sequencing is used to directly analyze the genomic DNA sequence of a particular gene. In general, only the parts of the ... in the DNA. Some examples of molecular diagnostic tests include DNA sequencing and Southern blotting.. College (4 yrs) → ... Southern blotting is an early technique basic on detection of fragments of DNA separated by size through gel electrophoresis ...
Single-cell DNA methylome sequencing quantifies DNA methylation. There are several known types of methylation that occur in ... Other methods to detect DNA methylation include methylation-sensitive restriction enzymes. Restriction enzymes also enable the ... as well as the limited amount of DNA extracted from a single cell. Due to scant amounts of DNA, accurate analysis of DNA poses ... July 2014). "The DNA methylation landscape of human early embryos". Nature. 511 (7511): 606-10. Bibcode:2014Natur.511..606G. ...
Within the eukaryotic genome are regions of DNA known as silencers. These DNA sequences bind to repressors to partially or ... Histone methylation/Histone methyltransferase *EZH2. *Histone demethylase. *Histone acetylation and deacetylation *Histone ... In molecular genetics, a repressor is a DNA- or RNA-binding protein that inhibits the expression of one or more genes by ... MetJ interacts with DNA bases via a ribbon-helix-helix (RHH) motif.[2] MetJ is a homodimer consisting of two monomers, which ...
... for DNA synthesis and RNA synthesis through methylation, and for preventing changes to DNA, thus for preventing cancer.[19] It ... 5-MTHF also plays both direct & indirect roles in DNA methylation, NO2 synthesis, and one-carbon metabolism.[52] ... This pathology results from persistently thwarted attempts at normal DNA replication, DNA repair, and cell division, and ... DNA production[edit]. Folate derivatives participate in the biosynthesis of both purines and pyrimidines. Formyl folate is ...
"Effects of histone acetylation and DNA methylation on p21( WAF1) regulation". World J. Gastroenterol. 8 (3): 400-5. doi:10.3748 ... and plays a regulatory role in S phase DNA replication and DNA damage repair.[17][18][19] Specifically, p21 has a high affinity ... not exposed to DNA damaging agents, have shown that DNA damage occurring in mother cell S-phase can induce p21 accumulation ... p21 acts as an effective inhibitor of DNA S-phase DNA synthesis though permits NER, leading to the proposal that p21 acts to ...
Together with similar modifications such as DNA methylation it is part of the epigenetic code.[1] Histones associate with DNA ... di-methylation repression[10] repression[3] repression[3] activation[9] tri-methylation activation[11] repression[8] repression ... "Histone methylation in DNA repair and clinical practice: new findings during the past 5-years". J Cancer. 9 (12): 2072-2081. ... Methylation of histone lysine also has a role in DNA repair.[5] For instance, H3K36me3 is required for homologous ...
Epigenetic promoter methylation in DNA repair genes in NSCLC Gene Frequency of hyper- (or hypo-) methylation DNA repair pathway ... DNA repair deficiency in NSCLC[edit]. Deficiencies in DNA repair underlie many forms of cancer.[21] If DNA repair is deficient ... "DNA Damage, Homology-Directed Repair, and DNA Methylation". PLOS Genetics. 3 (7): e110. doi:10.1371/journal.pgen.0030110. PMC ... In general, DNA damage appears to be the primary underlying cause of cancer.[18] Though most DNA damages are repairable,[17] ...
Because changes in cytosine methylation are correlated with gene regulation, the full DNA methylation maps allowed an ... Mitochondrial DNA analysisEdit. The mitochondrial DNA (mtDNA) from the finger bone discovered in Denisova Cave differs from ... The isolation and sequencing of nuclear DNA from the Denisova finger bone revealed an unusual degree of DNA preservation with ... "Reconstructing the DNA methylation maps of the Neandertal and the Denisovan". Science. 344 (6183): 523-27. Bibcode:2014Sci... ...
... such as cytosine methylation). This happens through the observation of polymerase kinetics. This approach allows reads of ... large DNA fragments into shorter DNA fragments. The fragmented DNA may then be cloned into a DNA vector and amplified in a ... DNA nanoball sequencing[edit]. Main article: DNA nanoball sequencing. DNA nanoball sequencing is a type of high throughput ... DNA sequencing may be used along with DNA profiling methods for forensic identification[4] and paternity testing. DNA testing ...
DNA methylation age. References[edit]. *^ Jabbari K, Bernardi G (May 2004). "Cytosine methylation and CpG, TpG (CpA) and TpA ... Methylation of CpG islands stably silences genes[edit]. In humans, DNA methylation occurs at the 5 position of the pyrimidine ... DNA damage appears to be the primary underlying cause of cancer.[39][40] If accurate DNA repair is deficient, DNA damages tend ... Main article: DNA methylation. CpG islands in promoters[edit]. In humans, about 70% of promoters located near the transcription ...
"Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation". Genes Dev. 13 ... DNA Cell Biol. 16 (4): 515-31. doi:10.1089/dna.1997.16.515. PMID 9150439.. ... The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res ...
DNA methylation is a process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA ... DNA methylation marks[edit]. DNA methylation marks - genomic regions with specific methylation pattern in a specific biological ... Ancient DNA methylation reconstruction, a method to reconstruct high-resolution DNA methylation from ancient DNA samples. The ... maintenance methylation and de novo methylation.[56] Maintenance methylation activity is necessary to preserve DNA methylation ...
... ... DNA methylation regulates the expression of genes that guide development and define cell types. In mammals, 70 to 80 percent of ... The DNA methylation signatures, called differentially methylated regions, that the researchers identified can be used to guide ... Charting a dynamic DNA methylation landscape of the human genome. Nature 500(7463):477-481. ...
... providing evidence that active transcription directly regulates DNA methylation levels. DNA methylation is an epigenetic ... RNAs are shown to interact with DNA methyltransferase 1 and prevent DNA methylation of genes at their specific locus, ... We identify a novel RNA arising from the CEBPA gene locus that is critical in regulating the local DNA methylation profile. ... A non-coding RNA arising from the well-studied methylation-sensitive gene CEBPA interacts with the DNA methyltransferase DNMT1 ...
... Brian H. Taylor BRIAN at BIO.TAMU.EDU Mon May 10 20:54:06 EST 1993 *Previous message: Poplar Molecular ... Im wondering if anyone has ever ruled out cytosine methylation at GC dinucleotides (as opposed to CG and CXG) or, for that ... Appropriate controls indicate that I dont have a problem with dirty DNA or bad enzyme or any of the usual trivial explanations ... 292, 860-862), where nearest neighbor analysis was used to show a high level of methylation at CG and CXG. One nonsymmetrical ...
NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol ... DNA methylation pat- terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell ... The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity. ... DNA Methylation and Cancer Therapy. Authors. * Moshe Szyf Series Title. Medical Intelligence Unit. Copyright. 2005. Publisher. ...
But DNA methylation of transgene usually leads to target gene silencing in plant genetic engineering. In this research,... ... DNA methylation plays an important role in gene expression in eukaryote. ... DNA methylation plays an important role in gene expression in eukaryote. But DNA methylation of transgene usually leads to ... and DNA methylation of promoter region was found. The results indicated that gene silencing might be caused by DNA methylation ...
DNA Methylation News and Research. RSS DNA methylation is a type of chemical modification of DNA that can be inherited and ... DNA methylation predicts survival outcome in patients with glioma A new study has shown that survival rates among patients with ... Scientists discover a small family of proteins that control inclusion of DNA methylation marks in genome Not all of your genome ... Researchers have shown that patients with spastic cerebral palsy (CP) can be identified using DNA methylation patterns in ...
DNA Methylation News and Research. RSS DNA methylation is a type of chemical modification of DNA that can be inherited and ... Asthmatics have lower degree of DNA methylation in certain immune cells Children with asthma have epigenetic DNA changes in ... Human airways already demonstrate gender-based differences in DNA methylation signatures at birth, providing an early hint of ... particularly an epigenetic change involving DNA methylation--arise from rogue cells escaping a natural cell deterioration ...
Single-cell analysis of mouse hematopoietic stem cells shows that mutations in DNA methylation genes change the frequencies of ... and support a model in which genome-wide methylation changes are transduced to differentiation skews through biases in CpG ... Mutations in genes involved in DNA methylation (DNAme; for example, TET2 and DNMT3A) are frequently observed in hematological ... DNA methylation dynamics during in vivo differentiation of blood and skin stem cells. Mol. Cell 47, 633-647 (2012). ...
Such methylation is probably part of a mechanism to permanently silence the activities of genes, including those on the inac … ... The methylation of CpG islands is often equated with transcriptional inactivity and there is overwhelming evidence that this is ... The DNA methylation paradox Trends Genet. 1999 Jan;15(1):34-7. doi: 10.1016/s0168-9525(98)01636-9. ... Such methylation is probably part of a mechanism to permanently silence the activities of genes, including those on the ...
DNA methylation is associated with histone modifications and the interplay of these epigenetic modifications is cr … ... DNA methylation is one of the most intensely studied epigenetic modifications in mammals. In normal cells, it assures the ... DNA methylation is reversible what makes it extremely interesting for therapy approaches. The importance of DNA methylation ... Apart from DNA methylation alterations in promoter regions and repetitive DNA sequences, this phenomenon is associated also ...
DNA methylation is probably universal in eukaryotes. In humans, approximately 1% of DNA bases undergo DNA methylation. In adult ... DNA methylation is a type of chemical modification of DNA that can be inherited without changing the DNA sequence. As such, it ... DNA methylation involves the addition of a methyl group to DNA for example, to the number 5 carbon of the cytosine pyrimidine ... DNA methylation typically occurs in a CpG dinucleotide context; non-CpG methylation is prevalent in embryonic stem cells.In ...
Now, scientists have developed a method to quickly couple methylation enzymes to their respective methylation pattern. This ... DNA methylation, which regulates vital cell functions, is still a big mystery to the scientific world. ... Scientists uncover mystery of DNA methylation To a large extent, DNA methylation, which regulates vital cell functions, is ... distinguish indigenous DNA from foreign DNA, or to mark old DNA strands during replication. Methylation is carried out by ...
Based on tracking DNA methylation, the new method could help doctors make decisions about preterm newborns care, or study ... It is based on tracking DNA methylation, a structural modification of DNA, whose patterns change as development progresses ... Gestational age measured via DNA methylation. Emory Health Sciences. Journal. Genome Biology. Funder. NIH/National Institute on ... The researchers also found that the difference between a newborns age predicted by DNA methylation and by an obstetrician may ...
Most DNA methylation is fixed for life from just a few weeks after conception. Lower levels of methylation have been linked to ... DNA methylation may be associated with health inequalities BMJ 2012; 344 :e722 ... The research focused on DNA methylation, the signalling tool that cells use to control gene expression and that is a crucial ... DNA methylation may be associated with health inequalities. BMJ 2012; 344 doi: (Published 31 ...
S2). The DNA methylation results were also confirmed by using methylation-specific PCR (Fig. 1C). Thus, the CpG island ... DNA methylation status was established by PCR analysis of bisulfite-modified genomic DNA, which induces chemical conversion of ... A microRNA DNA methylation signature for human cancer metastasis. Amaia Lujambio, George A. Calin, Alberto Villanueva, Santiago ... A microRNA DNA methylation signature for human cancer metastasis. Amaia Lujambio, George A. Calin, Alberto Villanueva, Santiago ...
DNA methylation affects the formation of active chromatin.. Keshet I, Lieman-Hurwitz J, Cedar H. ... To study the mechanism of gene repression by DNA methylation, M13 gene constructs were methylated to completion and inserted ... The results suggest that DNA methylation may exert its effect on gene transcription by altering both specific and nonspecific ... The use of micrococcal nuclease to probe for active or inactive supranucleosome particles also showed that DNA methylation ...
This kind of altered methylation or chemical add-on in as few as six sites in the landscape of methylated genes and DNA can be ... Methylation is a chemical change to DNA that can affect the ways genes are expressed and regulated.) ... In a study that correlated changes in DNA methylation (a chemical change that affects the level of gene expression) to changes ... "Just as we expected from our previous studies in one gene, this dysregulation between DNA methylation and gene expression when ...
IS10 transposition is regulated by DNA adenine methylation.. Roberts D, Hoopes BC, McClure WR, Kleckner N. ... Absence of methylation results in increased activity of both promoter and terminus, and completely accounts for increased ... IS10 has two dam methylation sites, one within the transposase promoter and one within the inner terminus where transposase ... Thus, in dam+ strains, IS10 will transpose preferentially when DNA is hemimethylated. We suggest specifically that IS10 ...
The pretreated DNA is amplified using at least one oligonucleotide primer, a polymerase and a set of nucleotides of which at ... An isolated genomic DNA sample is treated in a manner capable of distinguishing methylated from unmethylated cytosine bases. ... The method determines the level of methylation of a sample by measuring the extent of fluorescence resonance energy transfer ( ... Described is a method for methylation detection in a DNA sample. ... DNA Methylation. The levels of observation that have been ...
It has become apparent that the genomes of many organisms are characterized by unique patterns of DNA methylation which can ... Decreased Fidelity in Replicating DNA Methylation Patterns in Cancer Cells Leads to Dense Methylation of a CpG Island ... Thus, it is not surprising that studies on the role of DNA methylation now occupy center stage in many fields of biology and ... DNA Methylation: Development, Genetic Disease and Cancer. Editors: Doerfler, Walter, Böhm, Petra (Eds.) ...
Is the Fungus Magnaporthe Losing DNA Methylation?. Ken-ichi Ikeda, Ba Van Vu, Naoki Kadotani, Masaki Tanaka, Toshiki Murata, ... Is the Fungus Magnaporthe Losing DNA Methylation?. Ken-ichi Ikeda, Ba Van Vu, Naoki Kadotani, Masaki Tanaka, Toshiki Murata, ... Is the Fungus Magnaporthe Losing DNA Methylation?. Ken-ichi Ikeda, Ba Van Vu, Naoki Kadotani, Masaki Tanaka, Toshiki Murata, ...
DNA methylation dynamics regulate the formation of a regenerative wound epithelium during axolotl limb regeneration. *Aguilar C ... Aguilar, C., & Gardiner, D. M. (2015). DNA methylation dynamics regulate the formation of a regenerative wound epithelium ... We report a modulation of the expression DNMT3a, a de novo DNA methyltransferase, within the first 72 hours post injury that is ... Treatment of skin wounds on the upper forelimb with decitabine, a DNA methyltransferase inhibitor, induced changes in gene ...
... features that are not infrequently a consequence of Mendelian inheritance of mutations in genes involved in DNA methylation, ... histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation ... Genomic DNA Methylation Signatures Enable Concurrent Diagnosis and Clinical Genetic Variant Classification in ... Given the interrelated functions of these chromatin regulatory proteins, we sought to identify DNA methylation epi-signatures ...
... including DNA methylation. In this thesis, I analyze genome-scale DNA methylation profiles across pre-implantation development ... DNA methylation in early mammalian development. Author(s). Chan, Michelle M. (Michelle Mei Wah) ... In Chapter 1, I validate and refine the decades old model for DNA methylation in mouse embryogenesis, identify many ... In Chapter 2, 1 describe the DNA methylation dynamics in human preimplantation development and show that the regulatory ...
Pyrosequencing provides accurate and detailed profiles of DNA methylation patterns underlying cell cycle regulation, ... Now, the recently launched PyroMark Q24 Advanced system makes it easy to quantify methylation at non-CpG (CpN) sites commonly ... To characterize the methylation status of a DNA sequence via Pyrosequencing, the DNA is first incubated with sodium bisulfite. ... Pyrosequencing facilitates accurate DNA methylation analysis by: *Quantifying methylation in explicit sequence context ...
Richard Denison, Ph.D., is a Senior Scientist.. As a Washington policy geek, its sometimes hard not to let the ups and downs of political prospects for achieving real improvements in public health protections from toxic chemicals get me down. The tenacity with which some stakeholders insist on throwing wrenches into the works to block efforts to reach middle ground is indeed depressing.. But through it all, there is one constant that continually restores my optimism that well eventually get where we need to get to: Science keeps moving forward and inexorably points toward the need for reform. I will use this post to briefly highlight four recent studies that demonstrate the changing landscape of our knowledge of how environmental factors, including toxic chemical exposures, are affecting our health. Whats noteworthy about these studies is that they all identified adverse health effects in human populations, and linked those effects to early-life exposures. They all also illustrate the complex ...
... Mehrdad Ghavifekr Fakhr, Majid Farshdousti Hagh, Dariush ... Epigenetic modifications can affect the long-term gene expression without any change in nucleotide sequence of the DNA. ...
Plants grown in dry soil produce offspring that are hardier in drought conditions, and DNA methylation appears responsible. ... A long noncoding RNA associated with DNA methylation has the power to regulate colon cancer growth in vitro. ... After initially discovering that DNA methylation represses transcription, Howard Cedar continues to explore how the epigenetic ... The Role of DNA Base Modifications. By Skirmantas Kriaucionis , September 1, 2017 ...
The EZ DNA Methylation Kit uses a simplified procedure and streamlines the bisulfite method for DNA methylation analysis. The ... The EZ DNA Methylation Kits innovativ,biological,biology supply,biology supplies,biology product ... EZ-96 DNA Methylation Kit from Zymo Research. 2. EZ-96 DNA Methylation Kit - Deep Well from Zymo Research. 3. EZ-96 DNA ... The EZ DNA Methylation Kit uses a simplified procedure and streamlines the bisulfite method for DNA methylation analysis. The ...
  • [12] [16] By contrast, the genome of most plants, invertebrates, fungi, or protists show "mosaic" methylation patterns, where only specific genomic elements are targeted, and they are characterized by the alternation of methylated and unmethylated domains. (
  • Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. (
  • A Delaware team including Erin Crowgey, PhD, associate director of Bioinformatics with Nemours Biomedical Research, has published a study in the peer-reviewed journal BMC Bioinformatics, showing that DNA patterns in circulating blood cells can be used to help identify spastic cerebral palsy (CP) patients. (
  • Researchers have shown that patients with spastic cerebral palsy (CP) can be identified using DNA methylation patterns in circulating blood cells. (
  • Bird, A. DNA methylation patterns and epigenetic memory. (
  • Methylation is carried out by certain enzymes called methyltransferases, which decorate DNA with methyl groups in certain patterns to create an epigenetic layer on top of DNA. (
  • But in a new study, recently published in Nature Communications , scientists from The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain) at Technical University of Denmark have coupled enzymes with specific methylation patterns in two bacteria. (
  • But just as often, the host will reject the foreign DNA and chop it into pieces, simply because the methylation patterns reveal that the DNA is alien. (
  • In order to uncover this, the researchers constructed DNA-rings (plasmids) containing one of the methyltransferases and "cassettes" holding multiple copies of certain DNA patterns. (
  • These DNA-patterns, called motifs, are the targets for methyltransferases. (
  • This quick method of identifying methyltransferase methylation patterns holds great promise to other researchers struggling with DNA degradation, according to the research team. (
  • It is based on tracking DNA methylation, a structural modification of DNA, whose patterns change as development progresses before birth. (
  • This work extends upon earlier studies of DNA methylation patterns that change over development and predict age and age-related health conditions in children and adults. (
  • It has become apparent that the genomes of many organisms are characterized by unique patterns of DNA methylation which can differ from genome segment to genome segment and cell type to cell type. (
  • Pyrosequencing provides accurate and detailed profiles of DNA methylation patterns underlying cell cycle regulation, differential gene expression, and epigenetic effects. (
  • In addition, contiguous CpG sites are analyzed independently and within the same run, which enables assessment of sequence-wide methylation patterns while retaining details of position specific methylation (see figure Analysis of 16 CpG sites in a long sequence run ). (
  • Genomic methylation patterns are established in early embryos and are maintained during development through the interplay of demethylation mechanisms and the de novo and maintenance activities of DNA methyltransferases. (
  • DNA methylation is essential for mammalian development, and abnormal methylation patterns have been found in a great variety of human tumour cells. (
  • DNA methyltransferases reset the methylation patterns in early embryos and maintain their stability during development. (
  • Baubec T and Schubeler D (2014) Genomic patterns and context specific interpretation of DNA methylation. (
  • Perturbations of DNA methylation patterns are frequently associated with cancer and aging, raising a great interest in understanding the contribution of this mark to human health. (
  • Here we discuss commonly used wet-lab methodologies and computational approaches to identify DNA methylation patterns and measure their dynamics during biological processes in a quantitative and unbiased manner. (
  • DNA methylation patterns in newborns exposed to tobacco in utero," Journal of Translational Medicine , vol. 13, no. 1, article no. 25, 2015. (
  • To determine whether statins alter genomic methylation of DNA as a mechanism for modulation of gene expression, we propose to (Specific Aim I) study methylation patterns by comparing statin-treated, infected and non-treated cells, followed by (Specific Aim II) correlation of such changes in methylation with statins' modulation of gene expression. (
  • Based on previous studies illustrating that DNA methylation patterns in cancer cells are highly dependent on the organ in which the cancer originated, the team tested the tissue samples for DNA methylation. (
  • DNMT1 is constitutively expressed in proliferating cells and functions as a maintenance methyltransferase, transferring proper methylation patterns to newly synthesized DNA during replication. (
  • The authors acknowledge that analysis of leukocytes may not represent methylation patterns for all types of cells. (
  • DNA methylation plays a major role in epigenetic inheritance, because DNA methylation patterns can be stably inherited from cell to cell during mitosis, and in some cases from generation to generation during meiosis. (
  • The various types of DNMTs are responsible for the maintenance and establishment of DNA methylation patterns. (
  • Dnmt1 is the most abundant isoform in proliferating cells, displays a preference for hemimethylated substrates, and is targeted to replication forks, acting to maintain methylation patterns during cell replication ( Robertson, 2001 ). (
  • Studies in mammals suggest that environmental stimuli such as diet can alter the epigenetic state of the genome and affect gene expression by modifying DNA methylation and histone acetylation patterns ( 12 , 13 ). (
  • Two particular mechanisms, nucleosome occupancy and DNA methylation, have been reported to form specific patterns around promoters and these patterns were shown to correlate with gene expression ( Portela and Esteller, 2010 ). (
  • This book provides new research on the patterns, functions and roles in disease of DNA methylation. (
  • Chapter One studies the disruption of DNA methylation patterns caused by exposure to environmental factors during the developmental period. (
  • Chess and his team plan to use this technique to look for differences in methylation patterns between individuals with autism and healthy controls. (
  • Another useful feature of the methylation sites they are examining is that the patterns are similar regardless of whether the genes are turned on or off, so their impact on autism can be studied using easily accessible cells such as blood cells rather than requiring brain samples. (
  • some of the patterns that tend to occur in the way in which these epigenetic decorations to DNA occur correlate well with biological age. (
  • Patterns of methylation are programmed into the genome at birth, and they are known to change over a lifetime. (
  • The] methyl transferase system in humans is more complicated, but it will still be far easier to engineer a general increase in methylation than to copy youthful methylation patterns in detail. (
  • A line of evidence shows that these modified cytosines play a critical role in regulating gene function by impacting DNA methylation structures and patterns. (
  • MethTools' is a collection of software tools that replaces the time-consuming manual comparison process, generates graphical outputs of methylation patterns and methyl-ation density, estimates the systematic error of the experiment and searches for conserved methylated nucleotide patterns. (
  • Studies of DNA demethylation in differentiated cells suggests only a passive mechanism by which methylation patterns are lost during the DNA replication that occurs with each cellular division ( Ehrlich, 2003 ). (
  • In mammalian cells , the methylation process can be divided into two types carried out by two classes of DNA methyltransferases (DNMTs): maintenance methylation (to preserve DNA methylation after every cellular DNA replication cycle) and de novo methylation (to set up DNA methylation patterns early in development). (
  • The rates of enzymatic activity eventually drive the methylation process to a steady-state, resulting in the average methylation patterns observed in various cell types. (
  • n=39) methylation patterns. (
  • [8] DNA methylation as well as many of its contemporary DNA methyltransferases has been thought to evolve from early world primitive RNA methylation activity and is supported by several lines of evidence. (
  • DNA methyltransferases are responsible for establishing and maintenance of methylation pattern. (
  • In total, the two bacterial organisms hold 23 methyltranstransferase genes, but only show modification on 12 different DNA-motifs on their genomes, meaning that not all methyltransferases are active. (
  • Using this method, the team hopes to design hosts with an unambiguous "methylome" - meaning that the organism only harbours wanted methyltransferases, which will ease introduction of foreign DNA into non-model organisms. (
  • Baubec T, Colombo DF, Wirbelauer C et al (2015) Genomic profiling of DNA methyltransferases reveals a role for DNMT3B in genic methylation. (
  • DNA methylation is a reversible epigenetic mark involving the covalent transfer of a methyl group to the C-5 position of a cytosine residue by DNA methyltransferases (DNMTs), usually in the context of a cytosine-guanine dinucleotide (CpG) doublet. (
  • In neurons, as in other cells, DNA methylation and attendant changes in chromatin structure are driven by the actions of DNA methyltransferases (DNMTs). (
  • Three families of mammalian DNA methyltransferases have been identified: DNMT1, DNMT2 and DNMT3 (1,2). (
  • DNMT3A and DNMT3B function as de novo methyltransferases that methylate previously unmethylated regions of DNA. (
  • Nitric oxide (NO), produced by NOS2, enhanced enzymatic activity of DNA methyltransferases (DNMTs), methylation writers, and NO exposure induced minimal aberrant methylation. (
  • Cells rely on methyltransferases to recognize a specific DNA sequence and then attach a methyl group to one of its bases. (
  • DNA methylation was the first epigenetic mark to be discovered, involving the addition of a methyl group to the 5 position of cytosine by DNA methyltransferases, and can be inherited through cell division. (
  • DNA methyltransferases, or DNMTs, catalyze DNA methylation by adding methyl groups to the 5-carbon position of the cytosine ring, resulting in 5-methylcytosine. (
  • Epigenetic regulation thus facilitates the integration of intrinsic signals and environmental signals by using highly conserved enzymatic machinery that includes DNA cytosine-5-methyltransferases (Dnmts), histone deacetylases (HDAs), and methyl-binding proteins (MBPs) ( 18 ). (
  • DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor. (
  • DNA methylation occurs by the covalent addition of a methyl group at the 5-carbon of the cytosine ring by DNA methyltransferases, resulting in 5-methylcytosine (5-mC). (
  • In this study, we used genomic inhibition of DNA methylation through disruption of DNA methyltransferases DNMT1 and DNMT3B and pharmacologic inhibition with 5-Aza-2′-deoxycytidine (5-Aza-dC, decitabine) to demonstrate that DNA methylation predominantly regulates expression of metastasis-suppressive miRNAs in the 14q32 cluster. (
  • DNA methyltransferases (DNMTs) are the enzymes responsible for adding methyl groups at the 5-position of cytosine residues within CpG dinucleotides. (
  • DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting , X-chromosome inactivation , repression of transposable elements , aging , and carcinogenesis . (
  • Here we present data demonstrating that active transcription regulates levels of genomic methylation. (
  • The reason I am asking is that I occasionally encounter cases of possible incomplete digestion of restriction sites in genomic plant DNA with enzymes like HindIII (recognition sequence AAGCTT). (
  • We used a pharmacological and genomic approach to reveal this aberrant epigenetic silencing program by treating lymph node metastatic cancer cells with a DNA demethylating agent followed by hybridization to an expression microarray. (
  • An isolated genomic DNA sample is treated in a manner capable of distinguishing methylated from unmethylated cytosine bases. (
  • Genomic DNA Methylation Signature. (
  • 1992) A genomic sequencing protocol that yields a positive display of 5‐methylcytosine residues in individual DNA strands. (
  • Baubec T, Ivanek R, Lienert F, Schübeler D (2013) Methylation-dependent and -independent genomic targeting principles of the MBD protein family. (
  • CpGs by genomic sequencing of cloned single copy DNA confirmed heterogeneity in both these sublines. (
  • In particular, the methylation of clusters of methylation sites, called "CpG islands", near promoters and other gene regulatory elements may contribute to the stable silencing of genes, for example, during epigenetic processes such as genomic imprinting and X-chromosome inactivation. (
  • In the bulk of genomic DNA, most CpGs are methylated, whereas those located in a CpG island (where CpG sites cluster to form repetitive sequences) remain largely unmethylated ( 7 ). (
  • Background: Methylation of DNA at cytosine residues in mammalian cells is a heritable, epigenetic modification that is critical for proper regulation of gene expression, genomic imprinting and development (1,2). (
  • In addition, hypomethylation of bulk genomic DNA correlates with and may contribute to the onset of cancer. (
  • In mammalian cells, DNA methylation is generally associated with gene silencing and effects numerous cellular processes, including embryonic development, genomic imprinting, X-chromosome inactivation and preservation of chromosome stability. (
  • In contrast, a combination of TET knockdown and NO exposure synergistically induced aberrant methylation, involving genomic regions not methylated by either alone. (
  • This vicious combination was considered to cooperatively induce aberrant DNA methylation, even in genomic regions resistant to DNA methylation induction. (
  • Bisulfite conversion will work regardless of context, so the kits are compatible with genomic DNA derived from plants and other species with high non-CpG methylation levels. (
  • Following bisulfite treatment of genomic DNA, nonmethylated cytosine residues are converted into uracil. (
  • Researchers from Germany used the EZ DNA Methylation Kit to bisulfite convert genomic DNA from ex vivo isolated T cell subsets to study the changes in DNA methylation during differentiation of naïve T cells into Th cell subsets. (
  • The Bisulfite Genomic Sequencing technique has found wide acceptance for the generation of DNA-methylation maps with single-base resolution. (
  • Methylation maps are created by the comparison of bisulfite converted sequences with the untreated genomic sequence. (
  • Here, we show that DNA methyltransferase (DNMT) inhibition in hippocampal neurons results in activity-dependent demethylation of genomic DNA and a parallel decrease in the frequency of miniature EPSCs (mEPSCs), which in turn impacts neuronal excitability and network activity. (
  • In mammals, DNA methylation plays roles in many processes, such as X chromosome inactivation, genomic imprinting, and chromosome stability. (
  • By comparing the rates of methylation/demethylation of CpGs in different genomic locations, we found that rates could differ by two orders of magnitude for CpGs with similar steady-state measurements. (
  • However, the application of genome-wide approaches has allowed the analysis of DNA methylation in different genomic contexts revealing a more dynamic regulation than originally thought, since active DNA methylation and demethylation occur during cellular differentiation and tissue specification. (
  • DNA methylation is associated with histone modifications and the interplay of these epigenetic modifications is crucial to regulate the functioning of the genome by changing chromatin architecture. (
  • The changes include histone modifications, CpG island methylations and chromatin reorganizations which can cause the stable silencing or activation of particular genes. (
  • DNA methylation affects the formation of active chromatin. (
  • The mechanistic cross-talk between histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation signatures that are a reflection of those primary errors associated with chromatin dysregulation. (
  • Given the interrelated functions of these chromatin regulatory proteins, we sought to identify DNA methylation epi-signatures that could provide syndrome-specific biomarkers to complement standard clinical diagnostics. (
  • The methylation signal is interpreted by proteins capable of binding methylated CpGs and of recruiting histone epigenetic modificators, transcriptional corepressors and chromatin remodellers. (
  • Epigenetic modifications of chromatin and DNA are relevant for eukaryotic gene expression. (
  • This Review summarizes the TCGA DNA methylation findings to date, focusing on the molecular features of CpG island methylator phenotypes (CIMPs) shared among cancer types, the relationship between DNA methylation profiles and chromatin modifiers, and epigenetic silencing of key driver genes of carcinogenesis. (
  • DNA methylation changes protein-DNA interactions that lead to alterations in chromatin structure and rate of transcription ( Jones and Takai, 2001 ). (
  • In contrast, homologous recombination (HR), postreplicative repair, DNA helicases, and chromatin maintenance factors protect yeast cells against the cytotoxicity of this chemical. (
  • Post-transcriptional silencing of a neomycin phosphotransferase II transgene correlates with the accumulation of unproductive RNAs and with increase cytosine methylation of 3′-flanking regions, Plant J., 1997, 12(2): 379. (
  • Fig. 6: Single-cell multiomics links enhancer methylation and transcriptional priming, and identifies transcriptional priming skews within a human clonal hematopoiesis sample. (
  • The methylation of CpG islands is often equated with transcriptional inactivity and there is overwhelming evidence that this is the case for islands located in gene promoters. (
  • This has given rise to an interesting paradox in which methylation in the transcribed region is often correlated with expression, in contrast to the inverse correlation seen at the site of transcriptional initiation. (
  • This is the result of different transcriptional programs, which are partly controlled by epigenetic modifications, including DNA methylation. (
  • DNA methylation is the paradigm epigenetic modification that is associated with transcriptional repression. (
  • Transcriptional silencing of the DNA repair protein, O6-methylguanine-DNA methyltransferase (MGMT), occurs only in malignant or transformed cell lines, and such MGMT-deficient cells are hypersensitive to chemotherapeutic alkylating agents such as 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU) and temozolomide. (
  • DNMT1, DNMT3A and DNMT3B together form a protein complex that interacts with histone deacetylases (HDAC1, HDAC2, Sin3A), transcriptional repressor proteins (RB, TAZ-1) and heterochromatin proteins (HP1, SUV39H1), to maintain proper levels of DNA methylation and facilitate gene silencing (3-8). (
  • This study now reveals that methylation turnover increases with transcriptional activity and that the high overall methylation observed at genes is in constant flux as a function of transcription. (
  • DNA methylation of CpG islands within the promoter regions of tumor-suppressor genes is known to inhibit transcriptional initiation, and thereby silence these genes. (
  • Since then, the importance of DNA methylation in modulating transcriptional programs during development and differentiation processes has been strongly supported by many studies. (
  • compared transcriptional profiles using DNA microarrays to survey differentially expressed genes between parthenotes (2 maternal genomes) and control fetuses (1 maternal, 1 paternal genome). (
  • On this occasion, it doesn't involve miracle species or the like, but rather the results obtained by the University of Cordoba BIO301 research team called "Epigenetics and DNA Repair. (
  • Smoking during pregnancy profoundly changes both DNA and the expression of placental genes, a possible factor in physical changes that can last a lifetime, said researchers from Baylor College of Medicine in a report in the current edition of the journal Epigenetics. (
  • Use methylation-sensitive enzymes to explore epigenetics heritable changes in gene expression-that affect flowering in Arabidopsis . (
  • She continued, "Based on recent studies showing a role for epigenetics in RA and other autoimmune disorders, we hypothesised that epigenetic changes, such as DNA methylation, may provide potential biomarkers of response to anti-TNFs. (
  • Epigenetics is defined as heritable changes in gene expression which are not associated with changes in the sequence of the DNA. (
  • By coupling the two, the methyltransferase expressed by the plasmid would mark the DNA in a specific way, thus, revealing the enzyme's methylation pattern. (
  • We report a modulation of the expression DNMT3a, a de novo DNA methyltransferase, within the first 72 hours post injury that is dependent on nerve signaling. (
  • Treatment of skin wounds on the upper forelimb with decitabine, a DNA methyltransferase inhibitor, induced changes in gene expression and cellular behavior associated with a regenerative response. (
  • Inhibiting DNA methyltransferase (DNMT) activity, either by using the small-molecule inhibitor RG108 or by knocking down Dnmt1 and Dnmt3a , induced synaptic upscaling to a similar magnitude as exposure to TTX. (
  • DNA methyltransferase enzymes (DNMTs) catalyze the transfer of a methyl group from S-adenosyl methionine to the 5'-position of cytosines. (
  • We found that prolonged inhibition of DNA methyltransferase (DNMT) activity increased intrinsic membrane excitability of cultured cortical pyramidal neurons. (
  • In their system, DNA binding of artificial zinc finger proteins (shown, green) brings together two fragments (orange) of methyltransferase, which then assemble into the active enzyme. (
  • These methylation restriction systems are composed of specific DNA methyltransferase enzymes that act at short, palindromic sequences and restriction enzymes that cleave this same sequence only if it is unmethylated. (
  • DNA methylation is an epigenetic mechanism for gene silencing engaged by DNA methyltransferase (Dnmt)-catalyzed methyl group transfer to cytosine residues in gene-regulatory regions. (
  • The results suggest that DNA methylation may exert its effect on gene transcription by altering both specific and nonspecific interactions between DNA and nuclear proteins. (
  • Our data suggest that DNA methylation status controls transcription-dependent regulation of glutamatergic synaptic homeostasis. (
  • Our results suggest that DNA methylation in Apis is used for storing epigenetic information, that the use of that information can be differentially altered by nutritional input, and that the flexibility of epigenetic modifications underpins, profound shifts in developmental fates, with massive implications for reproductive and behavioral status. (
  • Global DNA methylation profiling reveals new insights into epigenetically deregulated protein coding and long noncoding RNAs in CLL. (
  • Specifically, we examined global DNA methylation changes in scions of cucumber, melon and watermelon heterografted onto pumpkin rootstocks using MSAP analysis. (
  • We observed a significant increase of global DNA methylation in cucumber and melon scions pointing to an epigenetic effect in Cucurbitaceae heterografting. (
  • Global DNA Methylation Assay Kit (5 Methyl Cytosine, Colorimetric) (ab233486) contains all reagents necessary for the quantification of global DNA methylation. (
  • It has been well demonstrated that the decrease in global DNA methylation is one of the most important characteristics of cancer. (
  • DNA methylation is a process by which methyl groups are added to the DNA molecule. (
  • DNA methylation involves the addition of a methyl group to DNA for example, to the number 5 carbon of the cytosine pyrimidine ring. (
  • All species mark their DNA with methyl groups. (
  • The methyl groups of the complementary methylated CpGs protrude into the major groove of the DNA molecule. (
  • The transfer of one-carbon methyl groups to nitrogen or oxygen (N- and O- methylation , respectively) to amino acid side chains increases the hydrophobicity of the protein and can neutralize a negative amino acid charge when bound to carboxylic acids. (
  • DNA methylation is a process by which methyl groups are added to the DNA molecule, especially at the 5 carbon of the cytosine ring, which forms 5-methylcytosine (5mC) ( 7 ). (
  • Well, DNA methylation refers to a particular methyl group binding to CpG sites in the genome. (
  • The enzyme subsequently transfers a methyl group to a cytosine in the region between the two DNA binding sites. (
  • For example, global decrease in 5-methylcytosine content (DNA hypomethylation) is likely caused by methyl-deficiency due to a variety of environmental influences, and has been proposed as a molecular marker in multiple biological processes such as cancer. (
  • Dnmt2 transfers methyl groups to RNA, not DNA ( Schaefer and Lyko, 2010 ). (
  • Andrew Chess and his colleagues at Massachusetts General Hospital are exploring a new way by which polymorphisms can control gene regulation - by influencing the addition of methyl groups to the DNA strand, impeding its expression. (
  • Addition of methyl groups to DNA. (
  • DNA is decorated with methyl groups , small molecular add-ons that act like "Do Not Disturb" signs for the underlying gene. (
  • Cytosine methylation occurs after DNA synthesis by enzymatic transfer of a methyl group from the methyl donor S -adenosylmethionine to the carbon-5 position of cytosine. (
  • In plants and other organisms, DNA methylation is found in three different sequence contexts: CG (or CpG ), CHG or CHH (where H correspond to A, T or C). In mammals however, DNA methylation is almost exclusively found in CpG dinucleotides, with the cytosines on both strands being usually methylated. (
  • Loss of amino-groups occurs with a high frequency for cytosines, with different consequences depending on their methylation. (
  • Cytosine methylation is widespread in both eukaryotes and prokaryotes, even though the rate of cytosine DNA methylation can differ greatly between species: 14% of cytosines are methylated in Arabidopsis thaliana, 4% to 8% in Physarum, 7.6% in Mus musculus, 2.3% in Escherichia coli, 0.03% in Drosophila, 0.006% in Dictyostelium and virtually none (0.0002 to 0.0003%) in Caenorhabditis or fungi such as Saccharomyces cerevisiae and S. pombe (but not N. crassa). (
  • non-CpG methylation is prevalent in embryonic stem cells.In plants, cytosines are methylated both symmetrically (CpG or CpNpG) and asymmetrically (CpNpNp), where N can be any nucleotide. (
  • The methylation status of specific cytosines can be determined using methods based on bisulfite sequencing. (
  • The kit is designed to reduce template degradation, minimize DNA loss during treatment and clean-up, and result in the complete conversion of unmethylated cytosines. (
  • Here we document a reporter gene-silencing event in Nicotiana tabacum that has a distinctive combination of features--i.e., (i) silencing occurs by a posttranscriptional process, (ii) silencing correlates with DNA methylation, and (iii) this de novo methylation is not restricted to cytosines located in the symmetrical motifs CG and CXG. (
  • Three DNA hypomethylation mutants of the flowering plant Arabidopsis thaliana were isolated by screening mutagenized populations for plants containing centromeric repetitive DNA arrays susceptible to digestion by a restriction endonuclease that was sensitive to methylated cytosines. (
  • De novo" DNMTs (DNMT3a and 3b) methylate cytosines on a single DNA strand, for example, at novel previously unmethylated sites in the genome. (
  • Following bisulfite conversion of the DNA, an epigenome-wide association study was conducted using the HumanMethylation450 BeadChip (Illumina) to determine unmethylated versus methylated cytosines within the DNA. (
  • Inhibition of the methylation of cytosines in the DNA of cultured cortical neurons enhanced their intrinsic membrane excitability so that the neurons generated more action potentials in response to a stimulus. (
  • For many years, evidence has been accumulating suggesting that methylation of cytosines in the DNA of animals, plants and fungi is involved in gene silencing. (
  • It occurs most frequently at cytosines that are followed by guanines (CpG), where high levels of DNA methylation in promoter regions are typically associated with gene repression. (
  • Built-in controls for the bisulfite treatment eliminate manual estimation of non-converted DNA levels and prevent false-positive methylation detection, thereby ensuring the reliability of results. (
  • To characterize the methylation status of a DNA sequence via Pyrosequencing, the DNA is first incubated with sodium bisulfite. (
  • With unique DNA Protect technology, QIAGEN EpiTect Bisulfite Kits facilitate complete conversion and minimal degradation of the treated DNA. (
  • The EZ DNA Methylation Kit uses a simplified procedure and streamlines the bisulfite method for DNA methylation analysis. (
  • We present a statistical model to describe allele-specific methylation (ASM) in data from high-throughput short-read bisulfite sequencing. (
  • Bisulfite and sodium bisulfite based techniques, often known as bisulfite conversion, are common approaches for preparing DNA for gene-specific DNA methylation analysis. (
  • Treatment of DNA with bisulfite converts cytosine to uracil while leaving 5-methylcytosine intact, allowing for single-nucleotide resolution information about the methylated areas of DNA. (
  • Popular methods for analyzing DNA methylation on a gene-specific basis, after bisulfite treatment, include bisulfite sequencing, methylation specific PCR, and methylation-based microarrays. (
  • Researchers have demonstrated that an alpha-hemolysin nanopore can identify epigenetic modifications of DNA, suggesting that eventually, nanopores will be able to perform single-molecule methylation sequencing of a DNA strand - an advance over current methylation sequencing methods, such as bisulfite sequencing, which require the DNA to be modified or amplified. (
  • Streamlined, proven procedure for bisulfite conversion of DNA. (
  • Desulphonation and recovery of bisulfite-treated DNA with a spin column. (
  • The EZ DNA Methylation Kit features a simplified procedure that streamlines bisulfite treatment of DNA. (
  • The EZ DNA Methylation Kit is based on the three-step reaction that takes place between cytosine and sodium bisulfite during which cytosine is converted into uracil. (
  • Q3: Which polymerase is recommended for amplification from bisulfite converted DNA? (
  • ZymoTaq DNA Polymerase has been specifically designed for use in bisulfite amplification reactions. (
  • Use a value of 40 μg/ml for Ab260 = 1.0 when determining the concentration of the recovered bisulfite-treated DNA. (
  • Q8: How long is bisulfite converted DNA stable at -20 °C? (
  • Minimize freeze/thawing to keep the bisulfite converted DNA stable. (
  • Desulphonation and recovery of bisulfite-treated DNA with a 96-well spin-column plate. (
  • The EZ-96 DNA Methylation Kits are bisulfite conversion kits that feature a high-throughput (96-well spin-plate), simplified procedure that streamlines bisulfite conversion of DNA. (
  • In-solution hybrid capture of bisulfite-converted DNA for targeted bisulfite sequencing of 174 ADME genes. (
  • This can be determined by bisulfite treatment of DNA, which converts cytosine residues to uracil but leaves methylated cytosine unaffected. (
  • RNA-directed histone and/or DNA modification is a conserved mechanism for the establishment of epigenetic marks from yeasts and plants to mammals. (
  • It is an epigenetic process that involves DNA methylation and histone methylation without altering the genetic sequence. (
  • Thus, it is not surprising that studies on the role of DNA methylation now occupy center stage in many fields of biology and medicine such as developmental biology, genetic imprinting, genetic disease, tumor biology, gene therapy, cloning of organisms and others. (
  • The project is expected to contribute to understanding of the possible role of DNA methylation as marker of exposure to carcinogenic exposure among WTC responders. (
  • Here, we will discuss the DNA methylation events that impact metabolism and the functional roles of DNMTs and TET proteins in adipose biology, with an emphasis on those that may be associated with obesity and T2D. (
  • DNA methylation is mediated by DNMTs. (
  • DNMT1 is the maintenance Dnmt for replication, whereas DNMT3a and -3b are referred as de novo DNMTs, as they can establish a new DNA methylation pattern ( 11 ). (
  • The DNMT3-like protein Dnmt3L is homologous to the other Dnmt3s but lacks catalytic activity, and Dnmt2 has sequence homology to all Dnmts but methylates cytoplasmic tRNA instead of DNA ( 11 ). (
  • It is commonly known that inactivation of certain tumor-suppressor genes occurs as a consequence of hypermethylation within the promoter regions and a numerous studies have demonstrated a broad range of genes silenced by DNA methylation in different cancer types. (
  • Apart from DNA methylation alterations in promoter regions and repetitive DNA sequences, this phenomenon is associated also with regulation of expression of noncoding RNAs such as microRNAs that may play role in tumor suppression. (
  • Our findings indicate that DNA methylation-associated silencing of tumor suppressor miRNAs contributes to the development of human cancer metastasis. (
  • This technology has been used to correlate DNA methylation to tumor type and gene expression, to measure cellular response to treatment with demethylating agents, and to assess changes in methylation state in relation to tumorigenesis, genetic imprinting, and exposure to environmental toxins (1). (
  • In 1999, Issa and colleagues first described a distinct subset of human colorectal cancers with extensive DNA hypermethylation of a subset of CpG islands that remained unmethylated in the remaining colorectal tumors ( 30 ) and are therefore distinguished from general cancer-specific DNA methylation for a specific tumor type (Figure 1 ). (
  • Epigenetic silencing of genes by a chemical modification called DNA methylation is known to play a role in the development of malignancies such as ovarian cancer by turning off genes that normally suppress tumor growth. (
  • Numerous studies have demonstrated tumor-specific alterations in DNA recovered from plasma or serum of patients with various malignancies, a finding that has potential for molecular diagnosis and prognosis. (
  • Aberrant DNA methylation of various tumor-suppressor genes is suggested to be correlates with biological features and clinical outcome of HCC ( 6 , 7 ). (
  • We screened for genes with promoter DNA hypermethylation using a genome-wide methylation microarray analysis in primary HCC tumors by comparison with their non-tumor tissue counterparts. (
  • The new CpN mode of the PyroMark Q24 Advanced system now enables methylation analysis of cytosine residues that are not part of CpG sites. (
  • The three types of PRMTs share the ability to mono-methylate arginine residues, but vary in their ability to generate differential methylation states (1-3). (
  • The building blocks of DNA (called CpGs), consist of about a half million positions in the genome. (
  • Smoking appears to have the strongest impact on the health of the genome and of the 58 CpGs found by the researchers, these DNA building blocks when altered were all associated with many different diseases. (
  • In fact, researchers found that 22 out of the 58 CpGs were previously associated with methylation caused by smoking in earlier studies. (
  • In other regions along the genome nucleosome occupancy is statistically independent of the positioning of CpGs or their methylation levels. (
  • Researchers from the Schübeler group now quantified actual rates of methylation and demethylation for 860,404 individual CpGs in mouse embryonic stem cells. (
  • They combined genetic ablations of methylating and demethylating enzymes with high-coverage quantitative measurements of DNA methylation and sophisticated modelling in order to quantify actual rates of methylation and demethylation for individual CpGs at the scale of the genome. (
  • Paternal genome demethylation includes the majority of CpGs, though methylation is maintained at several notable features4-7. (
  • We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell (ESC) derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of persistent maintenance are primarily restricted to gene bodies. (
  • To a large extent, DNA methylation, which regulates vital cell functions, is still a mystery to the scientific world. (
  • After initially discovering that DNA methylation represses transcription, Howard Cedar continues to explore how the epigenetic mark regulates gene expression. (
  • Publication date: Available online 17 February 2020Source: Neuroscience &Biobehavioral ReviewsAuthor(s): Charlotte A.M. Cecil, Yuning Zhang, Tobias NolteAbstractDNA methylation (DNAm) - an epigenetic process that regulates gene expression - may represent a mechanism for the biological embedding of early traumatic experiences, including childhood maltreatment. (
  • DNA methylation seems to be promising in putative translational use in patients and hypermethylated promoters may serve as biomarkers. (
  • Bestor TH, Edwards JR and Boulard M (2015) Notes on the role of dynamic DNA methylation in mammalian development. (
  • DNA methylation is an essential epigenetic modification for mammalian development and is crucial for the establishment and maintenance of cellular identity. (
  • We hypothesize that this type of synaptic plasticity may be critical for long-term memory storage within cortical circuits, a process that may also depend on epigenetic mechanisms, such as covalent chemical modification of DNA. (
  • Induction of epigenetic alterations, especially aberrant DNA methylation, is one of the major mechanisms, but how it is induced is still unclear. (
  • During the last decades, aberrant epigenetic mechanisms including DNA methylation have emerged as important components in cancer development. (
  • Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. (
  • Thus, motor neurons can engage epigenetic mechanisms to drive apoptosis, involving Dnmt upregulation and increased DNA methylation. (
  • This review outlines the published data regarding DNA methylation changes along the skeletal muscle program, in both physiological and pathological conditions, to better understand the epigenetic mechanisms that control myogenesis. (
  • MicroRNAs and DNA methylation are both critical epigenetic mechanisms for the control of gene expression. (
  • In this thesis, I analyze genome-scale DNA methylation profiles across pre-implantation development to identify the targets and characterize the dynamics of global demethylation that lead to totipotency and the subsequent changes to embryonic specification. (
  • We found that DNA cytosine demethylation mediates multiplicative synaptic upscaling of glutamatergic synaptic strength in cultured cortical neurons. (
  • NEW YORK (GenomeWeb) - DNA methylation reprogramming within embryos is a balance between widespread demethylation and targeted remethylation, a new single-cell study has found. (
  • DNA demethylation facilitated CCCTC-binding factor (CTCF) recruitment to the maternally expressed gene 3 differentially methylated region (MEG3-DMR), which acts as a cis -regulatory element for 14q32 miRNA expression. (
  • These results uncover a means by which NMDA receptor-mediated synaptic activity drives DNA demethylation within mature neurons and suppresses basal synaptic function. (
  • Conversely, DNA methylation can be lost either by incomplete maintenance following replication, referred to as passive demethylation, or actively via specific enzymes called TETs. (
  • Now, researchers from the Schübeler group, led by postdoc Paul Ginno, computational biologist Dimos Gaidatzis and former Ph.D. student Angelika Feldmann studied all three processes-de novo and maintenance methylation, as well as active demethylation-in mouse embryonic stem cells. (
  • The near-universal replacement of uracil by thymine in DNA, but not RNA, may have evolved as an error-control mechanism, to facilitate the removal of uracils generated by the spontaneous deamination of cytosine. (
  • Such methylation is probably part of a mechanism to permanently silence the activities of genes, including those on the inactive X chromosome. (
  • Even if silencing of a gene is initiated by another mechanism, this often is followed by methylation of CpG sites in the promoter CpG island to stabilize the silencing of the gene. (
  • To study the mechanism of gene repression by DNA methylation, M13 gene constructs were methylated to completion and inserted into mouse L cells by DNA-mediated gene transfer. (
  • DNA methylation is a powerful and extensively investigated epigenetic mechanism. (
  • The "maintenance" DNMT (DNMT1) recognizes a hemimethylated C-G dinucleotide (meaning, methylated on only one strand of DNA by a de novo DNMT) and converts the complementary C-G on the opposite strand into a methylated C-G. Through this mechanism, DNA can be perpetually methylated in the face of ongoing turnover of molecular marks. (
  • For this reason, many years ago, Francis Crick proposed that a self-perpetuating biochemical autoconversion of methylated DNA might serve as a memory mechanism at the molecular level ( 3 , 4 ). (
  • The project aims at correlating a detailed assessment of exposure of World Trade Center (WTC) responders enrolled at program at Stony Brook with alterations the mechanism of regulation of DNA called methylation, which may be relevant to cancer risk. (
  • The heterochromation formation in yeast is mediated by RNAi-directed silencing mechanism, while the establishment of DNA methylation in plants is through the RNA-directed DNA methylation (RdDM) pathway. (
  • In eukaryotic organisms, DNA methylation has evolved into a mechanism that allows dividing cells to stably inherit states of gene activity. (
  • The researchers plan to explore whether and how a mechanism involving polymorphisms and methylation might be at work in autism. (
  • DNA methylation is an epigenetic mechanism that plays a critical role in the repression of gene expression. (
  • DNA methylation is a key cellular mechanism used to repress gene expression and promote genome stability in various species. (
  • Epigenetic modifications of DNA are thought to be a mechanism by which gene expression is altered, resulting in changes in phenotypic traits. (
  • This misincorporated base will not be corrected during DNA replication as thymine is a DNA base. (
  • The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo- Edular biologists. (
  • This is done to regulate gene expression, distinguish indigenous DNA from foreign DNA, or to mark old DNA strands during replication. (
  • CpG islands (CGI) are regions of approximately 1 kb, which colocalise with the origins of DNA replication and with the promoters of about 70% of all genes. (
  • The great majority of CpG islands colocalise with transcription initiation sites and the origins of DNA replication. (
  • Delgado S, Gómez M, Bird A and Antequera F (1998) Initiation of DNA replication at CpG islands in mammalian chromosomes. (
  • One hypothesis stipulates that binding of mismatch repair (MMR) proteins to Me G/T mispairs arising during DNA replication triggers cell-cycle arrest and cell death. (
  • Methods: We meta-analyzed associations between exposure to PM10 (n=1,949) and PM2.5 (n=1,551) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. (
  • These results speak for a model where many transcription factors rebind DNA quickly after the replication fork, interfering with maintenance methylation. (
  • In this study, an international team of researchers from the United States and Japan performed a genome-wide analysis of gene expression in ovarian cancer by transcriptome profiling, looking for genes silenced by DNA methylation that might be involved in the disease. (
  • Standard methylation analysis methods provide only qualitative or semi-quantitative data, which can lead to inaccurate conclusions regarding the effects of epigenetic DNA methylation on cell cycle and metabolism. (
  • The group employed AI-based methods to analyze DNA methylation data from several hundred head and neck and lung cancers in order to train a deep neural network to distinguish between the two types of cancer. (
  • MethTools--a toolbox to visualize and analyze DNA methylation data. (
  • This should not be methylated by the usual rules, but if either GC or CXXG methylation occurs it would block digestion. (
  • Tet2 KO and Dnmt3a KO promote differential methylation of accessible transcription factor binding sites, favoring CpG-rich erythroid motifs. (
  • For genes with evidence of differential methylation and expression, 61% showed inverse relationships between these two properties, which is consistent with the concept that average decreases in methylation yield increases in gene expression. (
  • The methylation levels showed an inverse correlation to gene expression levels analyzed by real-time quantitative PCR. (
  • The analysis of methylation status exploits the quantitative nature of Pyrosequencing data. (
  • Genome-wide methylation profiles reveal quantitative views of human aging rates," Molecular Cell , vol. 49, no. 2, pp. 359-367, 2013. (
  • Methylated DNA immunoprecipitation (meDIP) is a large scale antibody-based technique that is used to enrich and capture methylated DNA fragments for use in gene-specific DNA methylation studies on a genome wide scale. (
  • I'm wondering if anyone has ever ruled out cytosine methylation at GC dinucleotides (as opposed to CG and CXG) or, for that matter, CXXG. (
  • In mammals, around 75% of CpG dinucleotides are methylated in somatic cells, and DNA methylation appears as a default state that has to be specifically excluded from defined locations. (
  • Three‐dimensional structure of a double‐stranded DNA fragment containing four methylated CpG dinucleotides. (
  • Methylation at CpG dinucleotides is a chemical modification of DNA hypothesized to play important roles in regulating gene expression. (
  • In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell type-specific regulation directed by DNA binding factors1-3. (
  • Most studies of DNA methylation have focused on discrete clusters at the beginning of genes, but Chess and colleagues are looking more broadly at methylation near polymorphisms throughout the genome. (
  • Longitudinal, genome-scale analysis of DNA methylation in twins from birth to 18 months of age reveals rapid epigenetic change in early life and pair-specific effects of discordance," Genome Biology , vol. 14, no. 5, article R42, 2013. (
  • Despite this reduction in DNA methylation levels, ddm1 mutants developed normally and exhibited no striking morphological phenotypes. (
  • The importance of DNA methylation alterations in tumorigenesis encourages us to decode the human epigenome. (
  • This notion has been borne out by a recent epigenome-wide association study that linked alterations in DNA methylation to whole-body insulin sensitivity ( 6 ). (
  • Thus, we have summarized all published information regarding alcohol-mediated alterations in DNA methylation during gestation. (
  • High-throughput sequencing allows interrogating the status of methylated DNA at nucleotide resolution and genome-wide, bringing unprecedented views on the distribution and dynamics of this relevant modification in healthy and diseased tissues. (
  • DNA methylation is one of many epigenetic marks that are often measured with high throughput technology, such as next-generation sequencing or microarrays. (
  • Using MethyLight, a high-throughput DNA methylation assay, we analyzed 39 genes in a gene evaluation set, consisting of 10 sera from metastasized patients, 26 patients with primary breast cancer, and 10 control patients. (
  • DNA methylation in cancer plays a variety of roles, helping to change the healthy regulation of gene expression to a disease pattern. (
  • And DNA methylation is a major determinant of so-called epigenetic gene regulation. (
  • DNA methylation plays an important role in normal human development and is associated with the regulation of gene expression, tumorigenesis, and other genetic and epigenetic diseases. (
  • These findings implicate epigenetic modification via DNA methylation in the regulation of metastatic propensity through miRNA networks and identify a previously unrecognized action of decitabine on the activation of metastasis-suppressive miRNAs. (
  • Patients of all three syndromes manifest levels of mental retardation, demonstrating the importance for proper DNA methylation in the regulation of normal brain function. (
  • DNA methylation is an essential epigenetic mark in eukaryotes and plays a role in gene regulation . (
  • When located in a gene promoter , DNA methylation typically acts to repress gene transcription . (
  • Figure 4: Transcription impedes DNA methylation. (
  • Gene silencing mediated by promoter homology occur at the level of transcription and results in meiotically heritable alterations in methylation and gene activity, Plant J., 1996, 9(2): 183. (
  • These data show that DNAme shapes the topography of hematopoietic differentiation, and support a model in which genome-wide methylation changes are transduced to differentiation skews through biases in CpG enrichment of the transcription factor binding motif. (
  • Competition between DNA methylation and transcription factors determines binding of NRF1. (
  • Methylation of CpG islands downstream of transcription initiation does not block elongation in mammalian cells. (
  • The methylation paradox might be resolved if it is hypothesized that transcription through a CpG island facilitates de novo methylation. (
  • Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. (
  • CpG-rich areas in promoters are one of the initiation sites where transcription factors bind to the DNA allowing transcription of the corresponding gene. (
  • When these regulatory regions are methylated, transcription factors are unable to bind DNA, thus inhibiting gene transcription ( Kimura and Shiota, 2003 ). (
  • Previously, nucleosome depleted regions were observed upstream of transcription start sites and nucleosome occupancy was reported to correlate both with CpG density and the level of CpG methylation. (
  • Another important finding of the study-which has recently been published in Nature Communications -suggests that transcription factor binding not only hinders de novo methylation, but also represents a challenge for maintenance methylation. (
  • DNA methylation dynamics regulate. (
  • In Chapter 2, 1 describe the DNA methylation dynamics in human preimplantation development and show that the regulatory principles that operate in mouse are conserved, though some of their targets are species-specific and define regions of local divergence. (
  • Finally, in Chapter 3, I compare DNA methylation dynamics of fertilization to an artificial reprogramming process, somatic cell nuclear transfer, in mouse, and find that most dynamics are conserved but occur at a smaller magnitude after artificial reprogramming. (
  • While the first genome-wide DNA methylation map in mammalian cells was established over 10 years ago, such maps only provide snapshots and do not inform about the actual dynamics of this epigenetic mark. (
  • While most features share similar dynamics to mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island (CGI) promoters that extend beyond known Imprint Control Regions (ICRs). (
  • The article [[Epigenetic inactivation of the premature aging Werner syndrome gene in human cancer] indicates the DNA repair gene WRN has a promoter that is frequently hypermethylated in a number of cancers, with hypermethylation occurring in 11% to 38% of colorectal, head and neck, stomach, prostate, breast, thyroid, non-Hodgkin lymphoma, chondrosarcoma and osteosarcoma cancers (see WRN). (
  • As discussed by Jin and Roberston in their review, silencing of a DNA repair gene by hypermethylation may be a very early step in progression to cancer. (
  • DNA hypermethylation in gene promoter regions is a frequent event in every human cancer and can inversely correlate with gene expression (reviewed in refs. (
  • We aimed to identify novel genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC). (
  • We screened for genes with promoter DNA hypermethylation using a genome-wide methylation microarray analysis in primary HCC (the discovery set). (
  • Further methylation analyses, combined with expression analyses, revealed novel genes that were downregulated by aberrant promoter hypermethylation in HCC. (
  • They also showed that DNA hypermethylation (DNA modification without changing sequence) plays a significant role in these processes. (
  • In the etanercept study, four CpG* sites showed differential DNA methylation that passed a false discovery rate of 0.05, while in the adalimumab study less significant results were observed. (
  • They nominate ~7600 genes with altered methylation with a false discovery rate of 0.05. (
  • We find the observed correlation between nucleosome occupancy and CpG density, respectively CpG methylation, to be specific to promoter regions. (
  • At a molecular level, methylation of DNA plays important roles in regulating overall gene expression. (
  • Global quantification of DNA methylation is crucial for understanding the roles that gene expression and silencing play in the development of cancer and other diseases. (
  • The aim of the research was to determine if higher levels of methylation had any correlation to mortality. (
  • If the results confirm a correlation between WTC exposures, assessed through a high-quality methodology, and altered DNA methylation, they might lead to the development of strategies to identify WTC responders at increased risk of cancer and other chronic diseases. (
  • Technical validation of methylation at this site by pyrosequencing showed very good correlation (Spearmans r=0.8). (
  • Anti-correlation between CpG density and methylation level is however similarly strong in both regions. (
  • However, no correlation between the methylation status and gender, age or tobacco use could be found for BE or EAC. (
  • Without quantification of methylation levels, it is not possible to distinguish physiologically relevant methylation from background methylation. (
  • Pyrosequencing solves this limitation by generating highly reproducible quantification of methylation frequencies at individual consecutive CpG sites (see figures Pyrosequencing analysis of CpG methylation pattern in the RASSF1A gene and Linearity of methylation quantification by Pyrosequencing ). (
  • The recent explosion of interest in these two areas has led to the development of innovative strategies for the analysis of short RNAs and methylation status, with qPCR established as a leading method for quantification. (
  • This talk describes and evaluates the currently available methods used for the quantification of microRNAs and DNA methylation by qPCR and highlights what factors must be taken into consideration in order to achieve optimal data. (
  • Genome-wide methylation characterization by arrays in diagnostic T-ALL samples identified two distinct methylation subgroups denoted CIMP+ (CpG Island Methylator Phenotype high) and CIMP- (low). (
  • DNA methylation is probably universal in eukaryotes. (
  • DNA Methylation is a common epigenetic signaling tool that is is used to control gene expression in eukaryotes. (
  • Cytosine DNA methylation at the fifth position of the cytosine ring is the most prevalent modification of DNA found in eukaryotic organisms. (
  • The ddm1 mutations were used to demonstrate that de novo DNA methylation in vivo is slow. (
  • In Chapter 1, I validate and refine the decades old model for DNA methylation in mouse embryogenesis, identify many retrotransposons with active DNA methylation signatures at fertilization, and discover many, novel differentially methylated regions between the gametes that exist transiently during early development. (
  • Compared with TET3 knockdown alone or NOC18 treatment alone, their combination strongly induced aberrant DNA methylation in the HSC60 cells in a culture period-dependent manner. (
  • D ) A model of induction of aberrant DNA methylation by chronic inflammation. (
  • It is unknown whether aberrant DNA methylation can cause neurodegeneration. (
  • Because it is possible to detect these epigenetic alterations in the bloodstream of patients, we investigated whether aberrant DNA methylation in patient pretherapeutic sera is of prognostic significance in breast cancer. (