Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
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.
Promoter Regions, Genetic
DNA Modification Methylases
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)
The systematic study of the global gene expression changes due to EPIGENETIC PROCESSES and not due to DNA base sequence changes.
Long Interspersed Nucleotide Elements
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.
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)
Molecular Sequence Data
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.
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).
Polymerase Chain Reaction
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.
Gene Expression Regulation, Neoplastic
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, Long Noncoding
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.
5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
Sequence Analysis, DNA
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.
Cell Line, Tumor
A cell line derived from cultured tumor cells.
Death-Associated Protein Kinases
Tumor Suppressor Proteins
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.
Site-Specific DNA-Methyltransferase (Adenine-Specific)
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 126.96.36.199.
Genes, Tumor Suppressor
Cyclin-Dependent Kinase Inhibitor p16
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.
Gene Expression Regulation
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.
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.
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.
Reverse Transcriptase Polymerase Chain Reaction
Oligonucleotide Array Sequence Analysis
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.
Gene Expression Profiling
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
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.
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.
Cyclin-Dependent Kinase Inhibitor p15
An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.
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.
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.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
snRNP Core Proteins
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.
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.
Insulin-Like Growth Factor II
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.
Tumor Markers, Biological
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.
Glutathione S-Transferase pi
DNA Repair Enzymes
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
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.
An enzyme that catalyzes the transfer of methyl groups from S-adenosylmethionine to free carboxyl groups of a protein molecule forming methyl esters. EC 2.1.1.-.
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.
Chromosome regions that are loosely packaged and more accessible to RNA polymerases than HETEROCHROMATIN. These regions also stain differentially in CHROMOSOME BANDING preparations.
Jumonji Domain-Containing Histone Demethylases
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.
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 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.
Core Binding Factor Alpha 3 Subunit
Chromatin Assembly and Disassembly
A pyrimidine nucleoside that is composed of the base CYTOSINE linked to the five-carbon sugar D-RIBOSE.
Protein Processing, Post-Translational
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.
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.
Embryonic Stem Cells
Amino Acid Sequence
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.
Repetitive Sequences, Nucleic Acid
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 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.
Tumor Cells, Cultured
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.
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.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Gene Expression Regulation, Developmental
Polycomb Repressive Complex 2
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.
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.
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.
Transcription Initiation Site
The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.
Methyl-CpG-Binding Protein 2
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.
Gene Expression Regulation, Plant
Deoxyribonucleases, Type II Site-Specific
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 188.8.131.52.
Adaptor Proteins, Signal Transducing
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
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.
Chromosomal Proteins, Non-Histone
Chromosomes, Human, X
DNA Restriction Enzymes
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.
Dosage Compensation, Genetic
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.
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)
Tumor Suppressor Protein p14ARF
A gene product of the p16 tumor suppressor gene (GENES, P16). It antagonizes the function of MDM2 PROTEIN (which regulates P53 TUMOR SUPPRESSOR PROTEIN by targeting it for degradation). p14ARF is produced from the beta mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced alpha transcript, is CYCLIN-DEPENDENT KINASE INHIBITOR P16. Both p16 gene products have tumor suppressor functions.
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.
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.
X Chromosome Inactivation
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.
Loss of Heterozygosity
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).
A purine base and a fundamental unit of ADENINE NUCLEOTIDES.
RNA, Small Interfering
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.
Cell Transformation, Neoplastic
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.
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.
A thiol-containing amino acid formed by a demethylation of METHIONINE.
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.
A cyclin A subtype primarily found in male GERM CELLS. It may play a role in the passage of SPERMATOCYTES into meiosis I.
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)
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
The genetic complement of a plant (PLANTS) as represented in its DNA.
Histone Deacetylase Inhibitors
Compounds that inhibit HISTONE DEACETYLASES. This class of drugs may influence gene expression by increasing the level of acetylated HISTONES in specific CHROMATIN domains.
Receptors, Retinoic Acid
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).
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
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.
Genes, Intracisternal A-Particle
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.
Protein Structure, Tertiary
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.
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.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
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)
Genome-Wide Association Study
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.
Methylenetetrahydrofolate Reductase (NADPH2)
Transport proteins that carry specific substances in the blood or across cell membranes.
Short Interspersed Nucleotide Elements
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).
Any method used for determining the location of and relative distances between genes on a chromosome.
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.
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.
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.
Gene Expression Regulation, Enzymologic
Nucleic acid structures found on the 5' end of eukaryotic cellular and viral messenger RNA and some heterogeneous nuclear RNAs. These structures, which are positively charged, protect the above specified RNAs at their termini against attack by phosphatases and other nucleases and promote mRNA function at the level of initiation of translation. Analogs of the RNA caps (RNA CAP ANALOGS), which lack the positive charge, inhibit the initiation of protein synthesis.
DNA Transposable Elements
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.
A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).
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)
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
High-Throughput Nucleotide Sequencing
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.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION.
Folic Acid Deficiency
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)
Real-Time Polymerase Chain Reaction
Methods used for detecting the amplified DNA products from the polymerase chain reaction as they accumulate instead of at the end of the reaction.