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.
Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
Tracts of land completely surrounded by water.
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.
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.
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.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
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.
Inorganic salts of sulfurous acid.
Numerous islands in the Indian Ocean situated east of Madagascar, north to the Arabian Sea and east to Sri Lanka. Included are COMOROS (republic), MADAGASCAR (republic), Maldives (republic), MAURITIUS (parliamentary democracy), Pemba (administered by Tanzania), REUNION (a department of France), and SEYCHELLES (republic).
The islands of the Pacific Ocean divided into MICRONESIA; MELANESIA; and POLYNESIA (including NEW ZEALAND). The collective name Oceania includes the aforenamed islands, adding AUSTRALIA; NEW ZEALAND; and the Malay Archipelago (INDONESIA). (Webster's New Geographical Dictionary, 1988, p910, 880)
An enzyme that catalyzes the transfer of a methyl group from S-ADENOSYLMETHIONINE to the 5-position of CYTOSINE residues in DNA.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
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)
DNA present in neoplastic tissue.
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.
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.
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.
An island in the Gulf of St. Lawrence constituting a province of Canada in the eastern part of the country. It is very irregular in shape with many deep inlets. Its capital is Charlottetown. Discovered by the French in 1534 and originally named Ile Saint-Jean, it was renamed in 1799 in honor of Prince Edward, fourth son of George III and future father of Queen Victoria. (From Webster's New Geographical Dictionary, 1988, p981 & Room, Brewer's Dictionary of Names, 1992, p433)
Scattered islands in the Mediterranean Sea. The chief islands are the Balearic Islands (belong to Spain; Majorca and Minorca are among these), Corsica (belongs to France), Crete (belongs to Greece), CYPRUS (a republic), the Cyclades, Dodecanese and Ionian Islands (belong to Greece), MALTA (a republic), Sardinia and SICILY (belong to Italy). (From Webster's New Geographical Dictionary, 1988, p747)
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 pyrimidine base that is a fundamental unit of nucleic acids.
The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.
One of the Type II site-specific deoxyribonucleases (EC 3.1.21.4). 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.-.
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.
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).
A cell line derived from cultured tumor cells.
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)
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.
The systematic study of the global gene expression changes due to EPIGENETIC PROCESSES and not due to DNA base sequence changes.
A group of islands in the Lesser Antilles in the West Indies, the three main islands being St. Croix, St. Thomas, and St. John. The capital is Charlotte Amalie. Before 1917 the U.S. Virgin Islands were held by the Danish and called the Danish West Indies but the name was changed when the United States acquired them by purchase.
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 collective name for the islands of the Pacific Ocean northeast of Australia, including NEW CALEDONIA; VANUATU; New Hebrides, Solomon Islands, Admiralty Islands, Bismarck Archipelago, FIJI, etc. Melanesia (from the Greek melas, black + nesos, island) is so called from the black color of the natives who are generally considered to be descended originally from the Negroid Papuans and the Polynesians or Malays. (From Webster's New Geographical Dictionary, 1988, p748 & Room, Brewer's Dictionary of Names, 1992, p344)
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.
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.
An INK4 cyclin-dependent kinase inhibitor containing four ANKYRIN-LIKE REPEATS. INK4B is often inactivated by deletions, mutations, or hypermethylation in HEMATOLOGIC NEOPLASMS.
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.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The collective name for islands of the Pacific Ocean east of the Philippines, including the Mariana, PALAU, Caroline, Marshall, and Kiribati Islands. (From Webster's New Geographical Dictionary, 1988, p761 & Room, Brewer's Dictionary of Names, 1992, p350)
A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.
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.
Genes whose abnormal expression, or MUTATION are associated with the development, growth, or progression of NEOPLASMS.
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.
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.
The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.
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.
The science dealing with the earth and its life, especially the description of land, sea, and air and the distribution of plant and animal life, including humanity and human industries with reference to the mutual relations of these elements. (From Webster, 3d ed)
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 raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.
A group of four British islands and several islets in the English Channel off the coast of France. They are known to have been occupied prehistorically. They were a part of Normandy in 933 but were united to the British crown at the time of the Norman Conquest in 1066. Guernsey and Jersey originated noted breeds of cattle. (From Webster's New Geographical Dictionary, 1988, p242)
Any method used for determining the location of and relative distances between genes on a chromosome.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
One of the Indian Ocean Islands, east of Madagascar. Its capital is Saint-Denis. It was discovered in 1507 by the Portuguese and claimed by France in 1638. It was first colonized in 1662 as Isle de Bourbon but renamed Reunion in 1793. In 1946 it was made an overseas department of France. The name commemorates the reunion of the revolutionaries from Marseilles with the National Guard in Paris in 1792. (From Webster's New Geographical Dictionary, 1988, p1011; Room, Brewer's Dictionary of Names, 1992, p454; French Embassy)
A British colony in the Atlantic Islands, comprising two principal islands, East Falkland and West Falkland. Its capital is Stanley. Discovered in 1592, it was not occupied until the French settled there briefly in 1764. Later the English settled there but were expelled by the Spanish in 1770. The Falklands were claimed by Argentina but were occupied in 1833 by the British who, after an April 1982 invasion by Argentina, regained them in June. The islands were named by British Captain John Strong in 1690 for the fifth Viscount Falkland who financed Strong's expedition. The Spanish name for the islands, Malvinas, is from the French Malouins, inhabitants of St. Malo who attempted to colonize the islands in 1764. (From Webster's New Geographical Dictionary, 1988, p389 & Room, Brewer's Dictionary of Names, 1992, p182)
The collective name for the islands of the central Pacific Ocean, including the Austral Islands, Cook Islands, Easter Island, HAWAII; NEW ZEALAND; Phoenix Islands, PITCAIRN ISLAND; SAMOA; TONGA; Tuamotu Archipelago, Wake Island, and Wallis and Futuna Islands. Polynesians are of the Caucasoid race, but many are of mixed origin. Polynesia is from the Greek poly, many + nesos, island, with reference to the many islands in the group. (From Webster's New Geographical Dictionary, 1988, p966 & Room, Brewer's Dictionary of Names, 1992, p426)
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.
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.
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.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
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.
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.
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 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.
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).
The relationships of groups of organisms as reflected by their genetic makeup.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
Established cell cultures that have the potential to propagate indefinitely.
The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.
Methylases that are specific for CYTOSINE residues found on DNA.
Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.
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.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
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.
Tumors or cancer of the STOMACH.
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.
Formation of an acetyl derivative. (Stedman, 25th ed)
Tumors or cancer of the COLON.
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.
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.
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.
The region of DNA which borders the 5' end of a transcription unit and where a variety of regulatory sequences are located.
Genotypic differences observed among individuals in a population.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
An enzyme catalyzing the formation of AMP from adenine and phosphoribosylpyrophosphate. It can act as a salvage enzyme for recycling of adenine into nucleic acids. EC 2.4.2.7.
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.
The systematic study of the complete DNA sequences (GENOME) of organisms.
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.
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

Detailed methylation analysis of the glutathione S-transferase pi (GSTP1) gene in prostate cancer. (1/4270)

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)

Comparative sequence analysis of human minisatellites showing meiotic repeat instability. (2/4270)

The highly variable human minisatellites MS32 (D1S8), MS31A (D7S21), and CEB1 (D2S90) all show recombination-based repeat instability restricted to the germline. Mutation usually results in polar interallelic conversion or occasionally in crossovers, which, at MS32 at least, extend into DNA flanking the repeat array, defining a localized recombination hotspot and suggesting that cis-acting elements in flanking DNA can influence repeat instability. Therefore, comparative sequence analysis was performed to search for common flanking elements associated with these unstable loci. All three minisatellites are located in GC-rich DNA abundant in dispersed and tandem repetitive elements. There were no significant sequence similarities between different loci upstream of the unstable end of the repeat array. Only one of the three loci showed clear evidence for putative coding sequences near the minisatellite. No consistent patterns of thermal stability or DNA secondary structure were shared by DNA flanking these loci. This work extends previous data on the genomic environment of minisatellites. In addition, this work suggests that recombinational activity is not controlled by primary or secondary characteristics of the DNA sequence flanking the repeat array and is not obviously associated with gene promoters as seen in yeast.  (+info)

Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. (3/4270)

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. (4/4270)

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)

Chlamydia infections and heart disease linked through antigenic mimicry. (5/4270)

Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.  (+info)

Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. (6/4270)

BACKGROUND: Conventional cytologic analysis of sputum is an insensitive test for the diagnosis of non-small-cell lung cancer (NSCLC). We have recently demonstrated that polymerase chain reaction (PCR)-based molecular methods are more sensitive than cytologic analysis in diagnosing bladder cancer. In this study, we examined whether molecular assays could identify cancer cells in bronchoalveolar lavage (BAL) fluid. METHODS: Tumor-specific oncogene mutations, CpG-island methylation status, and microsatellite alterations in the DNA of cells in BAL fluid from 50 consecutive patients with resectable (stages I through IIIa) NSCLC were assessed by use of four PCR-based techniques. RESULTS: Of 50 tumors, 28 contained a p53 mutation, and the identical mutation was detected with a plaque hybridization assay in the BAL fluid of 39% (11 of 28) of the corresponding patients. Eight of 19 adenocarcinomas contained a K-ras mutation, and the identical mutation was detected with a mutation ligation assay in the BAL fluid of 50% (four of eight) of the corresponding patients. The p16 gene was methylated in 19 of 50 tumors, and methylated p16 alleles were detected in the BAL fluid of 63% (12 of 19) of the corresponding patients. Microsatellite instability in at least one marker was detected with a panel of 15 markers frequently altered in NSCLC in 23 of 50 tumors; the identical alteration was detected in the BAL fluid of 14% (three of 22) of the corresponding patients. When all four techniques were used, mutations or microsatellite instability was detected in the paired BAL fluid of 23 (53%) of the 43 patients with tumors carrying a genetic alteration. CONCLUSION: Although still limited by sensitivity, molecular diagnostic strategies can detect the presence of neoplastic cells in the proximal airway of patients with surgically resectable NSCLC.  (+info)

Genomic structure and expression of the mouse growth factor receptor related to tyrosine kinases (Ryk). (7/4270)

We report the genomic organization of the mouse orphan receptor related to tyrosine kinases (Ryk), a structurally unclassified member of the growth factor receptor family. The mouse RYK protein is encoded by 15 exons distributed over a minimum of 81 kilobases. Genomic DNA sequences encoding a variant protein tyrosine kinase ATP-binding motif characteristic of RYK are unexpectedly found in two separate exons. A feature of the gene is an unmethylated CpG island spanning exon 1 and flanking sequences, including a TATA box-containing putative promoter and single transcription start site. Immunohistochemical examination of RYK protein distribution revealed widespread but developmentally regulated expression, which was spatially restricted within particular adult organs. Quantitative reduction of Southern blotting stringency for the detection of Ryk-related sequences provided evidence for a retroprocessed mouse pseudogene and a more distantly related gene paralogue. Extensive cross-species reactivity of a mouse Ryk kinase subdomain probe and the cloning of a Ryk orthologue from Caenorhabditis elegans demonstrate that Ryk and its relatives encode widely conserved members of a novel receptor tyrosine kinase subfamily.  (+info)

Isolation of DNA fragments associated with methylated CpG islands in human adenocarcinomas of the lung using a methylated DNA binding column and denaturing gradient gel electrophoresis. (8/4270)

We have constructed a library of DNA fragments heavily methylated in human adenocarcinomas of the lung to permit the comprehensive isolation of methylated CpG islands in cancer. Heavily methylated genomic DNA fragments from tumors of nine male patients were enriched using a methylated DNA binding column and used for construction of the library. From this library, DNA fragments having properties of CpG islands were isolated on the basis of their reduced rate of strand dissociation during denaturing gradient gel electrophoresis. Approximately 1,000 clones, corresponding to 0.3% of the library were analyzed, and nine DNA fragments were identified as being associated with CpG islands that were methylated in tumor DNA. One CpG island was methylated specifically in tumor DNA, whereas the remaining eight CpG islands were methylated both in normal and tumor DNA derived from the same patients. Our results suggest that the number of CpG islands methylated specifically in tumors is not large. The library, which contains DNA fragments from methylated CpG islands comprehensively, is expected to be valuable when elucidating epigenetic processes involved in carcinogenesis.  (+info)

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 ...
TY - JOUR. T1 - Prognostic Significance of Gremlin1 (GREM1) Promoter CpG Island Hypermethylation in Clear Cell Renal Cell Carcinoma. AU - van Vlodrop, Iris J. H.. AU - Baldewijns, Marcella M. L.. AU - Smits, Kim M.. AU - Schouten, Leo J.. AU - van Neste, Leander. AU - Van Criekinge, Wim. AU - van Poppel, Hein. AU - Lerut, Evelyne. AU - Schuebel, Kornel E.. AU - Ahuja, Nita. AU - Herman, James G.. AU - de Bruine, Adriaan P.. AU - van Engeland, Manon. PY - 2010/2. Y1 - 2010/2. U2 - 10.2353/ajpath.2010.090442. DO - 10.2353/ajpath.2010.090442. M3 - Article. VL - 176. SP - 575. EP - 584. JO - American Journal of Pathology. JF - American Journal of Pathology. SN - 0002-9440. IS - 2. ER - ...
Background: The CpG island methylator phenotype (CIMP), characterised by widespread promoter methylation, is associated with microsatellite instability (MSI) and BRAF mutation in colorectal cancer. The independent effect of CIMP, MSI and BRAF mutation on prognosis remains uncertain.. Methods: Utilising 649 colon cancers (stage I-IV) in two independent cohort studies, we quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) as well as CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, and WRN by using MethyLight technology. We examined MSI, KRAS and BRAF status. Cox proportional hazard models computed hazard ratios (HRs) for colon cancer-specific and overall mortalities, adjusting for patient characteristics and tumoral molecular features.. Results: After adjustment for other predictors of patient survival, patients with CIMP-high cancers (126 (19%) tumours with ⩾6/8 methylated CIMP-specific promoters) experienced a ...
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).
Previous studies of hypermethylation in Barretts esophagus and EAC have been limited to the CDKN2A gene and have focused on the analysis of a very small number of samples from each patient with Barretts esophagus and/or esophageal adenocarcinoma. In this study, we have used an alternative approach that not only documents the occurrence of hypermethylation of four CpG islands (APC, CDH1, CDKN2A, and ESR1) but also provides the topological context in which this hypermethylation occurs in histologically defined areas of Barretts-associated EAC. Because this experimental approach by necessity involves the analysis of a large number of samples per patient, we have restricted the number of cases to six. Although the limited number of patients does not allow us to extrapolate on the general occurrence of hypermethylation of these four genes in Barretts-associated EAC, this alternative strategy revealed interesting trends.. Our results demonstrate two important points:. (a) Abnormal methylation ...
Previous studies of hypermethylation in Barretts esophagus and EAC have been limited to the CDKN2A gene and have focused on the analysis of a very small number of samples from each patient with Barretts esophagus and/or esophageal adenocarcinoma. In this study, we have used an alternative approach that not only documents the occurrence of hypermethylation of four CpG islands (APC, CDH1, CDKN2A, and ESR1) but also provides the topological context in which this hypermethylation occurs in histologically defined areas of Barretts-associated EAC. Because this experimental approach by necessity involves the analysis of a large number of samples per patient, we have restricted the number of cases to six. Although the limited number of patients does not allow us to extrapolate on the general occurrence of hypermethylation of these four genes in Barretts-associated EAC, this alternative strategy revealed interesting trends.. Our results demonstrate two important points:. (a) Abnormal methylation ...
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 ...
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 ...
Aberrant CpG methylation changes occurring during tumour progression include the loss (hypomethylation) and gain (hypermethylation) of methyl groups. control. We have therefore demonstrated the ability of this technique, the identification of CGI exhibiting altered methylation patterns (ICEAMP), to isolate tumour-specific methylated GC-rich sequences. This will allow a comprehensive identification of methylation changes during tumourigenesis and will lead to a better understanding of the processes involved. INTRODUCTION The aberrant methylation of CpG dinucleotides has been widely reported during tumourigenesis in a variety of cancers (for review see 1). The alterations identified and their consequences include the loss of methyl groups, which is thought to buy 931409-24-4 increase chromosomal instability (2). Alternatively, the gain of methyl groups, particularly in CpG islands [CGIs: GC-rich regions of the genome, ~1 kb in length, originally characterised due to their lack of methylation (3)], ...
The methylator phenotype (CIMP) in CRC was identified by Toyota and colleagues after selecting particular CpG islands (CpGis) that displayed methylation in cancer-specific manner (so-called MINT loci; ref. 2). This allowed to distinguish subgroups of CRCs with prominent number of methylated CpGis, specific molecular features (BRAF mutation and MSI), and preferential localization in the proximal colon (later called CIMP-high or CIMP1; refs. 1, 2). Subsequently, after screening methylation of 92 CpGis in 187 CRCs, a new CIMP-specific marker panel was proposed by Weisenberger and colleagues and further enriched with new markers by Ogino and colleagues (3, 4). Parallel to the searches for marker candidates, a subgroup of CRCs with less extensive CpGis methylation enriched for the KRAS mutants was revealed (CIMP-low or CIMP2; refs. 7, 29). Finally, non-CIMP tumors (CIMP-0) have been correlated with a frequent loss of heterozygosity (LOH) at 18q that is regarded as 1 of the signs of chromosomal ...
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 ...
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
The role of DNA methylation in the control of mammalian gene expression has been the subject of intensive research in recent years, partly due to the critical role of CpG island methylation in the inactivation of tumour suppressor genes during the development of cancer. However, this research has also helped elucidate the role that DNA methylation plays in normal cells. At present, it is also clear that DNA methylation forms an important part of the normal cell-regulatory processes that govern gene transcription. Methylation, targeted at CpG islands, is an important part of the mechanisms that govern X-chromosome inactivation; it is also essential for the maintenance of imprinted genes and, at least in some cases, is critical in determining the cell-type-specific expression patterns of genes. Study of these examples will be important in identifying the mechanisms that control targeting of DNA methylation and how these processes are disrupted during disease pathogenesis.. ...
The effect of CpG islands on transgene expression was first tested in cultured cells. In transient transfection it was demonstrated that CpG islands do not influence the expression of a transgene when not integrated into the genome. Even when integrated into the genome of cultured cells, CpG islands are not able to confer position-independent, copy number-dependent transgene expression, as confirmed by the analysis of individual cell lines. However, the results from bulk analysis of primary clones suggest that CpG islands improve the level of expression in cultured cells, and increase the proportion of highly expressing clones. Transgenic mice were used to study the effect of CpG islands on the level and pattern of transgene expression in vivo. Unexpectedly, from the nine transgenic lines generated, transgene expression was detected in only one line. In the rest of the lines transgene expression was silenced, and in these cases the transgene was densely methylated. In half of the silenced lines ...
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 ...
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
CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near transcription start sites and may be associated with promoter regions. Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the Cs in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over evolutionary time, methylated Cs tend to turn into Ts because of spontaneous deamination. The result is that CpGs are relatively rare unless there is selective pressure to keep them or a region is not methylated for some other reason, perhaps having to do with the regulation of gene expression. CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole.. The unmasked version of the track displays potential ...
CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near transcription start sites and may be associated with promoter regions. Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the Cs in such an arrangement tend to be methylated. This methylation helps distinguish the newly synthesized DNA strand from the parent strand, which aids in the final stages of DNA proofreading after duplication. However, over evolutionary time, methylated Cs tend to turn into Ts because of spontaneous deamination. The result is that CpGs are relatively rare unless there is selective pressure to keep them or a region is not methylated for some other reason, perhaps having to do with the regulation of gene expression. CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole.. The unmasked version of the track displays potential ...
The CpG island methylator phenotype (CIMP) is a newly described mechanism for carcinogenesis in colorectal carcinomas and adenomas characterized by methylation of multiple CpG islands. The causes of CIMP are unknown. We studied CIMP in hyperplastic polyps (HPs), with emphasis on patients with multip …
CpG islands (CGIs) function as promoters for approximately 60% of human genes. Most of these elements remain protected from CpG methylation, a prevalent epigenetic modification associated with transcriptional silencing. Here, we report that methylation-resistant CGI promoters are characterized by si …
title: DNA Methylation of Intragenic CpG Islands are Required for Differentiation from iPSC to NPC, doi: 10.1007/s12015-020-10041-6, category: Article
Another question, if a 200bp fragment of CpG island across part of promoter and part of exon1, does its methylation state could be representative the methylation state of the whole promter CpG islands(more than 1000bp long)? Does it necessary to detect methylation state of the whole promoter CpG islands? If not, which region is the best representative? And how to find it? For MSP method,how long fragment is appropriate for detection ...
Results The frequency of promoter methylation was 52% for p14, 44% for p15, 50% for p16, 56% for p21, 38% for p27, 8% for p53, 42% for p57, 36% for p73, and 44% for RB1 of 50 ESCC. CIMP+ was detected in 54% (27/50) of ESCC and 8% (4/50) of dysplastic tissues; no CIMP+ was present in normal epithelial tissues (p,0.001). The results show that promoter methylation of p14, p15, p16, p21, p27, p57 and p73 was far more common in ESCC samples with CIMP+ than those with CIMP−. A significant difference between CIMP status and TNM stage and metastasis was found in ESCC (p,0.05). Patients with ESCC with CIMP+ had poorer 4-year survival than those with CIMP−. ...
CpG islands are genome regions with an elevated Guanine + Cytosine content (GC content) and a higher CpG dinucleotide frequency than observed in the bulk genome. More than half of the human gene promoters colocalize with CpG islands and their methylation status has been shown to correlate with the expression level of the associated genes. As a consequence, CpG islands are assumed to be hotspots of epigenetic regulation.. However, an exact definition of CpG islands is still not agreed upon. The CgiHunter software tool follows the original sequence-based CpG island definition proposed by Gardiner-Garden and Frommer. They defined three requirements a genome region has to fulfill to qualify as a CpG island: a minimal length, a minimal GC content and a minimal ratio of its observed over its expected CpG dinucleotide frequency. Unlike many other heuristic-based approaches, the CgiHunter algorithm has been proven to identify all genome regions that meet a specified criteria and results in robust and ...
Cancer-specific hypermethylation of (promoter) CpG islands is common during the tumorigenesis of colon cancer. Although associations between certain genetic aberrations, such as BRAF mutation and microsatellite instability, and the CpG island methylator phenotype (CIMP), have been found, the mechanisms by which these associations are established are still unclear. We studied genome-wide DNA methylation differences between colorectal tumors carrying a BRAF mutation and BRAF wildtype tumors. ...
Mechanisms regulating mitochondrial DNA (mtDNA) amount according to developmental stage and tissue origin are still unknown. Recent works have suggested the role of epigenetic modification at a CpG island located in POLG gene, encoding the polymerase responsible for mtDNA synthesis. We found that this CpG island is highly methylated in human tissues, whatever developmental stages (after 12 weeks) or tissue energy-demand. This methylation level is not modified by the presence of genetic mutations that can alter the mtDNA amount (mtDNA or inactivating POLG mutations). Mechanisms involved in mtDNA amount control in human differenciated cells remain to be identified. (By Dr. Julie STEFFANN, http://jmg.bmj.com/content/early/2017/01/09/jmedgenet-2016-104335 ...
BACKGROUND: Methylation of CpG islands within the DNA promoter regions is one mechanism that leads to aberrant gene expression in cancer. In particular, the abnormal methylation of CpG islands may silence associated genes. Therefore, using high-throughput microarrays to measure CpG island methylation will lead to better understanding of tumor pathobiology and progression, while revealing potentially new biomarkers. We have examined a recently developed high-throughput technology for measuring genome-wide methylation patterns called mTACL. Here, we propose a computational pipeline for integrating gene expression and CpG island methylation profiles to identify epigenetically regulated genes for a panel of 45 breast cancer cell lines, which is widely used in the Integrative Cancer Biology Program (ICBP). The pipeline (i) reduces the dimensionality of the methylation data, (ii) associates the reduced methylation data with gene expression data, and (iii) ranks methylation-expression associations ...
There are so many CpG sites in one CpG island ,and the CpG sites investigated by a MSP are so limited. Only less than 10 CpG sites included in the two pairs of primers for MSP that can be investgated by a MSP. Why so little CpG sites mehtylation informatiom can repsent the whole CpG island ...
Genomic imprinting is a process that leads to the silencing of one allele of a gene in a parent of origin specific manner. Genes that are involved in this process are often regulated in clusters, one of which is the Peg3 (Paternally expressed gene 3) imprinted domain. We investigated this region for both CpG islands and long antisense transcripts, two common features of imprinted gene clusters. First, we performed a systematic survey of DNA methylation status of the CpG islands in this region of the mouse, cow, and human genomes. We identified two previously unreported differentially methylated regions (DMR): one in the promoter region of mouse Zim3 and another in the promoter region of human USP29. The PEG3-CpG island is the only DMR that is conserved among these three species. PEG3 has been implicated in several types of cancer, so we examined the methylation status of several CpG islands in this region using human tumor derived DNA. The CpG islands near PEG3 and USP29 both showed hypermethylation in
CpG dinucleotides are known to play a crucial role in regulatory domains, affecting gene expression in their natural context. Here, we demonstrate that intragenic CpG frequency and distribution impacts transgene and genomic gene expression levels in mammalian cells. As shown for the Macrophage Inflammatory Protein 1α, de novo RNA synthesis correlates with the number of CpG dinucleotides, whereas RNA splicing, stability, nuclear export and translation are not affected by the sequence modification. Differences in chromatin accessibility in vivo and altered nucleosome positioning in vitro suggest that increased CpG levels destabilize the chromatin structure. Moreover, enriched CpG levels correlate with increased RNA polymerase II elongation rates in vivo. Interestingly, elevated CpG levels particularly at the 5 end of the gene promote efficient transcription. We show that this is a genome-wide feature of highly expressed genes, by identifying a domain of ∼700 bp with high CpG content downstream of the
In addition to mutations, epigenetic silencing of genes has been recognized as a fundamental mechanism that promotes human carcinogenesis. To date, characterization of epigenetic gene silencing has largely focused on genes in which silencing is mediated by hypermethylation of promoter-associated CpG islands, associated with loss of the H3K4me3 chromatin mark. Far less is known about promoters lacking CpG-islands or genes that are repressed by alternative mechanisms. We performed integrative ChIP-chip, DNase-seq, and global gene expression analyses in colon cancer cells and normal colon mucosa to characterize chromatin features of both CpG-rich and CpG-poor promoters of genes that undergo silencing in colon cancer. Epigenetically repressed genes in colon cancer separate into two classes based on retention or loss of H3K4me3 at transcription start sites. Quantitatively, of transcriptionally repressed genes that lose H3K4me3 in colon cancer (K4-dependent genes), a large fraction actually lacks CpG islands.
All the human tissue specimens used in this study were obtained as part of our ongoing work aimed at characterizing molecular alterations in endometrial cancer. All participants consented to molecular analyses and follow-up. These protocols have been approved by the Washington University Medical Centers Human Studies Committee.. Differential methylation hybridization analysis. Procedures used for tissue DNA extraction have been described previously (15). Differential methylation hybridization (DMH) analysis was done using high-density slide arrays containing 7,776 CpG island clones (MseI CpG inserts) using 20 endometrial cancer (endometrioid histology, ,70% neoplastic cellularity) and three pooled normal endometrium DNAs as a reference control. Tumor and control amplicons were labeled with Cy5 and Cy3, respectively, and cohybridized onto microarray slides using our established protocols (16). Normalized Cy5/Cy3 hybridization intensities were calculated, and candidate loci with ratios ,1.5 were ...
DNA methylation in vertebrates typically occurs at CpG sites (cytosine-phosphate-guanine sites; that is, where a cytosine is directly followed by a guanine in the DNA sequence); this methylation results in the conversion of the cytosine to 5-methylcytosine. The formation of Me-CpG is catalyzed by the enzyme DNA methyltransferase. The bulk of mammalian DNA has about 40% of CpG sites methylated but there are certain areas, know as CpG islands which are GC rich (made up of about 65% CG residues) where none are methylated. These are associated with the promoters of 56% of mammalian genes, including all ubiquitously expressed genes. 1-2% of the human genome are CpG clusters and there is an inverse relationship between CpG methylation and transcriptional activity.. ...
Purpose: To carry out the mutation analysis of the KIF21A gene in a four-generation Indian family affected with CFEOM1 and to find out the molecular basis of the most frequent mutations c.2860C,T and c.2861G,A in exon 21 of the KIF21A gene. Methods: Mutational analysis was carried out by direct automated sequencing of the PCR products from exons 8, 20, and 21 of the KIF21A gene. Allele specific oligo hybridization analysis was carried out to study the segregation of the mutation within the family. Methylation status of the mutated CpG dinucleotide in exon 21 was detected using bisulfite genomic sequencing technique on genomic DNA isolated from blood and sperms. Results: We found a previously reported missense mutation c.2860C,T (p.954R,W) in exon 21 of the KIF21A gene in our family. This mutation was found in a CpG dinucleotide. Bisulfite genomic sequencing revealed that all the CpG dinucleotides in exon 21 including the one which harbored the two most frequent mutations were methylated both in ...
Fingerprint Dive into the research topics of CpG islands in human ZFX and ZFY and mouse Zfx Genes: Sequence similarities and methylation differences. Together they form a unique fingerprint. ...
Microbial DNA sequences containing unmethylated CpG dinucleotides activate Toll-like receptor 9 (TLR9). We have found that TLR9 is localized to the endoplasmic reticulum (ER) of dendritic cells (DCs) and macrophages. Because there is no precedent for immune receptor signaling in the ER, we investigated how TLR9 is activated. We show that CpG DNA binds directly to TLR9 in ligand-binding studies. CpG DNA moves into early endosomes and is subsequently transported to a tubular lysosomal compartment. Concurrent with the movement of CpG DNA in cells, TLR9 redistributes from the ER to CpG DNA-containing structures, which also accumulate MyD88. Our data indicate a previously unknown mechanism of cellular activation involving the recruitment of TLR9 from the ER to sites of CpG DNA uptake, where signal transduction is initiated.
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West DB, Engelhard EK, Adkisson M, Nava AJ, Kirov J, Cipollone A, Willis BJ, Rapp J, de Jong P, Lloyd KCK. Transcriptome analysis of targeted mouse mutations reveals the topography of local changes in gene expression. PLOS Genetics. 2016 Feb 3;12(2).. Lloyd KCK, Khanna C, Hendricks W, Trent J, and Kotlikoff M. Precision medicine: an opportunity for a paradigm shift in veterinary medicine. JAVMA. 2016;248:45-48.. Jong Pieter, West DB. Reporter gene silencing in targeted mouse mutants is associated with promoter CpG island methylation. PLoS One. 2015 Aug 14;10(8).. Karp NA, Meehan TF, Morgan H, Mason JC, Blake A, Kurbatova N, Smedley D, Jacobsen J, Mott JF, Iyer V, Matthews P, Melvin DG, Wells S, Flenniken AM, Masuya H, Wakana S, White JK, Lloyd KCK, Reynolds CL, Paylor R, West DB, Svenson KL, Chesler EJ, Hrab? de Angelis MH, Tocchini-Valentini GP, Sorg-Guss T, Herault Y, Parkinson H, Mallon A-M, Brown SD. Applying the ARRIVE guidelines to an in vivo database. PLoS Biol. 2015 May ...
In normal cells, DNA methylation is rare in promoter-associated CpG islands but important to X-inactivation, genomic imprinting and repression of repetitive ele...
Kaplan-Meier curves of cancer-specific survival of patients with pancreatic cancer according to CpG island methylator phenotype (CIMP) statusIn the Kaplan-M
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 ...
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 - 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 - 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 - 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 ...
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 ...
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 - Genome-wide analysis of promoter methylation associated with gene expression profile in pancreatic adenocarcinoma. AU - Vincent, Audrey. AU - Omura, Noriyuki. AU - Hong, Seung Mo. AU - Jaffe, Andrew. AU - Eshleman, James. AU - Goggins, Michael. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2011/7/1. Y1 - 2011/7/1. N2 - Purpose: The goal of this study was to comprehensively identify CpG island methylation alterations between pancreatic cancers and normal pancreata and their associated gene expression alterations. Experimental Design: We employed methylated CpG island amplification followed by CpG island microarray, a method previously validated for its accuracy and reproducibility, to analyze the methylation profile of 27,800 CpG islands covering 21 MB of the human genome in nine pairs of pancreatic cancer versus normal pancreatic epithelial tissues and in three matched pairs of pancreatic cancer versus lymphoid tissues from the same individual. Results: ...
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
Reduced representation bisulfite sequencing (RRBS) is an efficient and high-throughput technique used to analyze the genome-wide methylation profiles on a single nucleotide level. This technique combines restriction enzymes and bisulfite sequencing in order to enrich for the areas of the genome that have a high CpG content. Due to the high cost and depth of sequencing needed to analyze methylation status in the entire genome, Meissner et al. developed this technique in 2005 in order to reduce the amount of nucleotides needed to be sequenced to 1% of the genome. The fragments that comprise the reduced genome still include the majority of promoters, as well as regions such as repeated sequences that are difficult to profile using conventional bisulfite sequencing approaches. Enzyme digestion: First, genomic DNA is digested using a methylation-insensitive restriction enzyme. It is integral for the enzymes to not be influenced by the methylation status of the CpGs (sites within the genome where a ...
659 CpG islands showed significant loss or gain of methylation. Satellite and Alu sequences were primarily associated with loss of methylation, while promoter CpG islands composed the majority of sequences with gains in methylation. Since the majority of ovarian tumors are late stage when diagnosed, we tested whether DNA methylation profiles could differentiate between normal and low malignant potential (LMP) compared to stage III ovarian samples. We developed a class predictor consisting of three CpG-rich sequences that was 100% sensitive and 89% specific when used to predict an independent set of normal and LMP samples versus stage III samples. Bisulfite sequencing confirmed the NKX-2-3 promoter CpG island was hypermethylated with disease progression. In addition, 5-aza-2-deoxycytidine treatment of the ES2 and OVCAR ovarian cancer cell lines re-expressed NKX-2-3. Finally, we merged our CpG methylation results with previously published ovarian expression microarray data and identified ...
Epigenetic alterations are fundamental hallmarks of cancer genomes. We surveyed the landscape of DNA methylation alterations in gastric cancer by analyzing genome-wide CG dinucleotide (CpG) methylation profiles of 240 gastric cancers (203 tumors and 37 cell lines) and 94 matched normal gastric tissues. Cancer-specific epigenetic alterations were observed in 44% of CpGs, comprising both tumor hyper- and hypomethylation. Twenty-five percent of the methylation alterations were significantly associated with changes in tumor gene expression. Whereas most methylation-expression correlations were negative, several positively correlated methylation-expression interactions were also observed, associated with CpG sites exhibiting atypical transcription start site distances and gene body localization. Methylation clustering of the tumors revealed a CpG island methylator phenotype (CIMP) subgroup associated with widespread hypermethylation, young patient age, and adverse patient outcome in a disease ...
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, ...
We performed a genome-wide scan of 27,578 CpG loci covering 14,475 genes to identify differentially methylated loci (DML) in colorectal carcinoma (CRC). We used Illuminas Infinium methylation assay in paired DNA samples extracted from 24 fresh frozen CRC tissues and their corresponding normal colon tissues from 24 consecutive diagnosed patients at a tertiary medical center. We found a total of 627 DML in CRC covering 513 genes, of which 535 are novel DML covering 465 genes. We also validated the Illumina Infinium methylation data for top-ranking genes by non-bisulfite conversion q-PCR-based methyl profiler assay in a subset of the same samples. We also carried out integration of genome-wide copy number and expression microarray along with methylation profiling to see the functional effect of methylation. Gene Set Enrichment Analysis (GSEA) showed that among the major gene sets that are hypermethylated in CRC are the sets: inhibition of adenylate cyclase activity by G-protein signaling, Rac guanyl
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 ...
Although primary lymphomas of the central nervous system (PCNSL) and extracerebral diffuse large B-cell lymphoma (DLBCL) cannot be distinguished histologically, it is still a matter of debate whether PCNSL differ from systemic DLBCL with respect to their molecular features and pathogenesis. Analysis of the DNA methylation pattern might provide further data distinguishing these entities at a molecular level. Using an array-based technology we have assessed the DNA methylation status of 1,505 individual CpG loci in five PCNSL and compared the results to DNA methylation profiles of 49 DLBCL and ten hematopoietic controls. We identified 194 genes differentially methylated between PCNSL and normal controls. Interestingly, Polycomb target genes and genes with promoters showing a high CpG content were significantly enriched in the group of genes hypermethylated in PCNSL. However, PCNSL and systemic DLBCL did not differ in their methylation pattern. Based on the data presented here, PCNSL and DLBCL do not
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 ...
The expression of metallothionein (MT)-3 is often markedly reduced in gastric carcinoma (GC). The molecular mechanism of this MT-3 downregulation is unknown. Transcriptional silencing of MT-3 by methylation of CpG island was investigated by nucleotide sequencing and denaturing high performance liquid chromatography (DHPLC) analyses. We found that normal brain tissue and a xenografted GC that expressed MT-3 mRNA had unmethylated regions of the CpG island in intron1 of this gene. On the other hand, gastric cancer cell lines AGS and MKN445, a xenografted GC, and a representative primary gastric cancer that had no expression of MT-3 mRNA demonstrated hypermethylation of the MT-3 intron1 CpG island. Treatment of the gastric cancer cell lines with 5-azacytidine resulted in new expression of MT-3 mRNA in these cells. A quantifying DHPLC assay was developed to determine the methylation status of this specific region of the MT-3 gene.. Fifty-eight primary GC and their corresponding normal gastric ...
Environmental and genetic factors play an important role in the etiology of breast cancer. Several small blood-based DNA methylation studies have reported risk associations with methylation at individual CpGs and average methylation levels; however, these findings require validation in larger prospective cohort studies. To investigate the role of blood DNA methylation on breast cancer risk, we conducted a meta-analysis of four prospective cohort studies, including a total of 1663 incident cases and 1885 controls, the largest study of blood DNA methylation and breast cancer risk to date. We assessed associations with methylation at 365,145 CpGs present in the HumanMethylation450 (HM450K) Beadchip, after excluding CpGs that did not pass quality controls in all studies. Each of the four cohorts estimated odds ratios (ORs) and 95% confidence intervals (CI) for the association between each individual CpG and breast cancer risk. In addition, each study assessed the association between average methylation
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
DNA methylation is the most widely studied epigenetic mark and is known to be essential to normal development and frequently disrupted in disease. The Illumina HumanMethylation450 BeadChip assays the methylation status of CpGs at 485,577 sites across the genome. Here we present Subset-quantile Within Array Normalization (SWAN), a new method that substantially improves the results from this platform by reducing technical variation within and between arrays. SWAN is available in the minfi Bioconductor package.
DNA methylation is a well-balanced process in healthy cells. But in some diseases, cancers in particular, aberrant CpG methylation changes may occur, and both genomewide hypomethylation and gene-specific hypermethylation in promoters of tumor suppressor genes can be observed. |br /> |br /> Many studies have shown that tumor emergence and growth are associated with changes in DNA methylation patterns, such as in the case of prostate cancer development. Therefore, one of the most important application areas for epigenetic research is the diagnosis and treatment of cancer — using DNA methylation patterns to detect cancer at very early stages, to classify tumors, and to predict and monitor response to drug treatments. |br /> |br /> QIAGEN offers innovative tools to expediate methylation analysis — from detection to quantification. The new PyroMark Q24 Advanced allows quantitative methylation analysis at consecutive CpG or CpN sites. |br />  |br /> For high-throughput
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 ...
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
Reduced representation bisulfite sequencing (RRBS) was developed to measure DNA methylation of high-CG regions at single base-pair resolution, and has been widely used because of its minimal DNA requirements and cost efficacy; however, the CpG coverage of genomic regions is restricted and important regions with low-CG will be ignored in DNA methylation profiling. This method could be improved to generate a more comprehensive representation. Based on in silico simulation of enzyme digestion of human and mouse genomes, we have optimized the current single-enzyme RRBS by applying double enzyme digestion in the library construction to interrogate more representative regions. CpG coverage of genomic regions was considerably increased in both high-CG and low-CG regions using the double-enzyme RRBS method, leading to more accurate detection of their average methylation levels and identification of differential methylation regions between samples. We also applied this double-enzyme RRBS method to
Near promoters, both nucleosomes and CpG sites form characteristic spatial patterns. 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. Several studies imply a causal link where CpG methylation might induce nucleosome formation, whereas others argue the opposite, i.e. that nucleosome occupancy might influence CpG methylation. Correlations are indeed evident between nucleosomes, CpG density and CpG methylation - at least near promoter sites. It is however less established whether there is an immediate causal relation between nucleosome occupancy and the presence of CpG sites - or if nucleosome occupancy could be influenced by other factors. In this work, we test for such causality in human genomes by analyzing the three quantities both near and away from promoter sites. For data from the human genome we compare promoter regions with given CpG densities with
The aberrant methylation of CpG islands is a common epigenetic alteration found in cancers. The process contributes to cancer formation through the transcriptional silencing of tumor suppressor genes. CpG island methylation has been observed in aberrant crypt foci (ACF) and adenomas in the colon, implicating it in the earliest aspects of colon cancer formation. In addition, some investigators have identified an age-related increase in DNA methylation of the ESR1 locus in the colon mucosa, suggesting that DNA methylation may be a pre-neoplastic change that increases the risk of colon adenomas and colon cancer. We investigated the methylation status in the promoter regions of the CDKN2A/p16, hMLH1, and MGMT genes in human non-neoplastic rectal mucosa and evaluated whether these methylation markers may predict the presence of adenomatous polyps in the colon. The promoter methylation patterns of these genes were examined in rectal biopsies (mucosa samples) of 97 colorectal adenoma cases and 94 ...
Three methyl-CpG-binding domain (MBD) proteins in Arabidopsis, AtMBD5, AtMBD6, and AtMBD7, are functional in binding methylated CpG dinucleotides in vitro and localize to the highly CpG-methylated chromocenters in vivo. These proteins differ, however, in their subnuclear localization pattern; AtMBD5 and AtMBD6, each containing a single MBD motif, show preference for two perinucleolar chromocenters, whereas AtMBD7, a naturally occurring poly-MBD protein containing three MBD motifs, localizes to all chromocenters. Here we studied the significance of multiple MBD motifs for subnuclear localization and mobility in living cells. We found that the number of MBD motifs determines the subnuclear localization of the MBD protein. Furthermore, live kinetic experiments showed that AtMBD7-green fluorescent protein (GFP) has lower mobility than AtMBD5-GFP and AtMBD6-GFP, which is conferred by cooperative activity of its three MBD motifs. Thus, the number of MBD motifs appears to affect not only binding ...
Diagenodes Premium RRBS(Reduced representation bisulfite sequencing) kit obtained excellent results with almost 90% alignment rate, 4.1 million CpGs covered and bisulfite conversion rates around 99.5% for all samples
OBJECTIVE: To detect the status of methylation in promoter region of MEIS1 gene and its expression in cell lines and patients with HOX11(+) T-cell acute lymphoblastic leukemia (T-ALL) and explore the relationship between the expression level of MEIS1 gene and methylation of CpG island in promoter region. METHODS: The methylation pattern in MEIS1 gene was detected with bisulfite sequencing PCR, DNA methylation immunoprecipitation and promoter oligonucleotide microarray. And the expression level of MEIS1 mRNA was detected with reverse transcription PCR in 3 T-ALL cell lines: sil-ALL, DND41 and RPMI as well as in 75 clinical bone marrow samples including 38 de novo T-ALL patients, 29 complete remission T-ALL patients and 8 normal samples from January 2009 to December 2011. RESULTS: The expressions of HOX11 mRNA in the patients were classified into high expression (HOX11(+)) groups (n = 14) and low expression (HOX11(-)) groups (n = 24) . There was hypermethylation of CpG island in promoter region of ...
Purpose:To assess differentially methylated landscapes according to prostate cancer (PCa) Gleason score (GS) and ERG oncogene expression status, and to determine the extent of polycomb group (PcG) target gene involvement, we sought to assess the genome-wide DNA methylation profile of PCa according to GS and ERG expression. Experimental Design:Genomic DNA from 39 PCa specimens was hybridized to CpG island microarrays through differential methylation hybridization. We compared methylation profiles between GS and ERG expression status as well as GS stratified by ERG expression status. In addition, we compared results from our dataset to publicly available datasets of histone modifications in benign prostate cells. Results:We discovered hundreds of distinct differentially methylated regions (DMRs) associated with increasing GS and ERG. Furthermore, the number of DMRs associated with GS was greatly expanded by stratifying samples into ERG positive versus ERG negative, with ERG positive/GS ...
TY - CHAP. T1 - DNA Methylation Alterations in Human Cancers. AU - Kanai, Yae. AU - Arai, Eri. PY - 2012. Y1 - 2012. UR - http://www.scopus.com/inward/record.url?scp=84882534159&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84882534159&partnerID=8YFLogxK. 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 - ...
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 ...
Epigenetic alternation is a common contributing factor to neoplastic transformation. Although previous studies have reported a cluster of aberrant promoter methylation changes associated with silencing of tumor suppressor genes, little is known concerning their sequential DNA methylation changes during the carcinogenetic process. The aim of the present study was to address a genome-wide search for identifying potentially important methylated changes and investigate the onset and pattern of methylation changes during the progression of colorectal neoplasia. A three-phase design was employed in this study. In the screening phase, DNA methylation profile of 12 pairs of colorectal cancer (CRC) and adjacent normal tissues was analyzed by using the Illumina MethylationEPIC BeadChip. Significant CpG sites were selected based on a cross-validation analysis from The Cancer Genome Atlas (TCGA) database. Methylation levels of candidate CpGs were assessed using pyrosequencing in the training dataset (tumor lesions
TY - JOUR. T1 - Characterizing DNA methylation patterns in pancreatic cancer genome. AU - Tan, Aik-Choon. AU - Jimeno, Antonio. AU - Lin, Steven H.. AU - Wheelhouse, Jenna. AU - Chan, Fonda. AU - Solomon, Anna. AU - Rajeshkumar, N. V.. AU - Rubio-Viqueira, Belen. AU - Hidalgo, Manuel. PY - 2009/12/1. Y1 - 2009/12/1. N2 - We performed a global methylation profiling assay on 1505 CpG sites across 807 genes to characterize DNA methylation patterns in pancreatic cancer genome. We found 289 CpG sites that were differentially methylated in normal pancreas, pancreatic tumors and cancer cell lines. We identified 23 and 35 candidate genes that are regulated by hypermethylation and hypomethylation in pancreatic cancer, respectively. We also identified candidate methylation markers that alter the expression of genes critical to gemcitabine susceptibility in pancreatic cancer. These results indicate that aberrant DNA methylation is a frequent epigenetic event in pancreatic cancer; and by using global ...
Rationale: Hemodynamic disturbed flow is associated with susceptibility to atherosclerosis. Endothelial KLF4 is an important anti-inflammatory atheroprotective transcription factor that is suppressed in regions of disturbed flow. Objective: The plasticity of epigenomic KLF4 transcriptional regulation by flow-mediated DNA methylation was investigated in vitro and in arterial tissue. Methods and Results: To recapitulate dominant flow characteristics of atheroprotected and atherosusceptible arteries, human aortic endothelial cells (HAEC) were subjected to pulsatile undisturbed flow (UF) or oscillatory disturbed flow (DF) containing a flow-reversing phase. Differential CpG site methylation was measured by methylation specific PCR, bisulfite pyrosequencing and restriction enzyme-PCR. The methylation profiles of endothelium from disturbed and undisturbed flow sites of adult swine aortas were also investigated. In vitro, DF increased DNA methylation of CpG islands within the KLF4 promoter that ...
An increasing number of studies are using beadarrays to measure DNA methylation on a genome-wide basis. The purpose is to identify novel biomarkers in a wide range of complex genetic diseases including cancer. A common difficulty encountered in these studies is distinguishing true biomarkers from false positives. While statistical methods aimed at improving the feature selection step have been developed for gene expression, relatively few methods have been adapted to DNA methylation data, which is naturally beta-distributed. Here we explore and propose an innovative application of a recently developed variational Bayesian beta-mixture model (VBBMM) to the feature selection problem in the context of DNA methylation data generated from a highly popular beadarray technology. We demonstrate that VBBMM offers significant improvements in inference and feature selection in this type of data compared to an Expectation-Maximization (EM) algorithm, at a significantly reduced computational cost. We further ...
Provides some functions to detect and correct for batch effects in DNA methylation data. The core function BEclear is based on Latent Factor Models and can also be used to predict missing values in any other matrix containing real numbers.
Colorectal cancer (CRC) is one of the most common causes of cancer related deaths in western countries. CRC are commonly divided in cancers showing microsatellite stability (MSS) or microsatellite instability (MSI). A more novel classification is dependent on promoter hypermethylation of CpG islands (the CpG island methylator phenotype, CIMP), where cancers show high, low or negative methylation status. SMAD4, located on chromosome 18q, has been thoroughly investigated during the last years. Loss of SMAD4 expression has been reported to correlate with poor CRC patient prognosis. In this study we analyze the impact of SMAD4 expression on prognosis in relation to MSI screening status and CIMP status. 479 paraffin-embedded specimens of CRC were examined for nuclear SMAD4 expression using immunohistochemistry. The tumors were scored loss (-), moderate (+) and high (++) expressing tumors. Loss of SMAD4 correlated significantly with decreased survival in all colon cancer patients. High SMAD4 ...
Epigenetic deregulation has emerged as a driver in human malignancies. There is no clear understanding of the epigenetic alterations in hepatocellular carcinoma (HCC) and of the potential role of DNA methylation markers as prognostic biomarkers. Analysis of tumor tissue from 304 patients with HCC treated with surgical resection allowed us to generate a methylation-based prognostic signature using a training-validation scheme. Methylome profiling was done with the Illumina HumanMethylation450 array (Illumina, Inc., San Diego, CA), which covers 96% of known cytosine-phosphate-guanine (CpG) islands and 485,000 CpG, and transcriptome profiling was performed with Affymetrix Human Genome U219 Plate (Affymetrix, Inc., Santa Clara, CA) and miRNA Chip 2.0. Random survival forests enabled us to generate a methylation signature based on 36 methylation probes. We computed a risk score of mortality for each individual that accurately discriminated patient survival both in the training (221 patients; 47% ...
Memory efficient analysis of base resolution DNA methylation data in both the CpG and non-CpG sequence context. Integration of DNA methylation data derived from any methodology providing base- or low-resolution data.
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 ...
DNA methylation is a major epigenetic modification important for regulating gene expression and suppressing spurious transcription. Most methods to scan the genome in different tissues for differentially methylated sites have focused on the methylation of CpGs in CpG islands, which are concentrations of CpGs often associated with gene promoters. Here, we use a methylation profiling strategy that is predominantly responsive to methylation differences outside of CpG islands. The method compares the yield from two samples of size-selected fragments generated by a methylation-sensitive restriction enzyme. We then profile nine different normal tissues from two human donors relative to spleen using a custom array of genomic clones covering the euchromatic portion of human chromosome 1 and representing 8% of the human genome. We observe gross regional differences in methylation states across chromosome 1 between tissues from the same individual, with the most striking differences detected in the comparison of
DNA methylation of the CpG dinucleotide is one of the most crucial epigenetic modifications in mammals [1]. Its feature is a modification of the 5-position of the pyrimidine ring of cytosine that produces 5-methylcytosine (5mc). A large body of literature demonstrates that the level of genome-wide DNA methylation (also is referred to as overall DNA methylation) changes dynamically during the course of normal development, and this epigenetic regulation is critical in the determination of cell fate during embryogenesis [2, 3]. For example, during the preimplantation stage, the mammalian genome becomes progressively demethylated, which is associated with the initiation of cellular differentiation of somatic cells [3].. On the contrary, impairment of methylation can damage assorted aspects of gene regulation, such as X chromosome inactivation [1], genomic imprinting [4] and retroviral silencing [5]. Additionally, environmental factors, such as ionizing radiation [6] and hormone exposure [7], could ...
"CpG Island Info". genome.ucsc.edu. Retrieved 2020-05-03. Gardiner-Garden M, Frommer M (July 1987). "CpG islands in vertebrate ... The CpG island associated with this promoter has 75 CpGs (22% of island), and is 676bp long. The C count plus G count is 471, ... the percentage C or G is 70% within this island, and the ratio of observed to expected CpG is 0.91. As determined by ...
"Predicting aberrant CpG island methylation". Proceedings of the National Academy of Sciences. 100 (21): 12253-12258. doi: ...
... contain a CpG island. CpG islands are generally 200 to 2000 base pairs long, have a C:G base pair content >50%, and have ... and these frequently contain CpG islands as well. An example is the promoter of the DNA repair gene ERCC1, where the CpG island ... there are about 600 to 800 heavily methylated CpG islands in promoters of genes in the tumors while these CpG islands are not ... The presence of multiple methylated CpG sites in CpG islands of promoters causes stable inhibition (silencing) of genes. ...
"CpG islands. They showed that CpG islands are a distinct feature of vertebrate genomes and that CpG islands are associated with ... that the majority of neural and neuroendocrine genes were associated with CpG islands and therefore proposed that CpG islands ... CpG-rich DNA. Cell 40: 91-99. Gardiner-Garden, M. and Frommer, M. (1987). CpG islands in vertebrate genomes. J. Mol. Biol. 196 ... Gardiner-Garden, M. and Frommer, M. (1994). Transcripts and CpG islands associated with the pro-opiomelanocortin gene and other ...
... which in turn tend to cluster in regions called CpG islands. There is a small fraction of CpG islands that can overlap or be in ... February 2000). "Aberrant CpG-island methylation has non-random and tumour-type-specific patterns". Nat. Genet. 24 (2): 132-8. ... Gardiner-Garden M, Frommer M (July 1987). "CpG islands in vertebrate genomes". J. Mol. Biol. 196 (2): 261-82. doi:10.1016/0022- ... October 2002). "An AscI Boundary Library for the Studies of Genetic and Epigenetic Alterations in CpG Islands". Genome Res. 12 ...
... contain a CpG island (see CpG islands in promoters). If the initially nonmethylated CpG sites in a CpG island become largely ... the CpG islands that control promoters tend to gain methylation with age. The gain of methylation at CpG islands in promoter ... of CpG cytosines are methylated. However, in vertebrates there are CpG islands, about 300 to 3,000 base pairs long, with ... These CpG islands are predominantly nonmethylated. In humans, about 70% of promoters located near the transcription start site ...
Toyota M, Ahuja N, Ohe-Toyota M, Herman JG, Baylin SB, Issa JP (July 1999). "CpG island methylator phenotype in colorectal ... Thus, mutations in IDH1 and IDH2 generate a "DNA CpG island methylator phenotype or CIMP" that causes promoter hypermethylation ... Nazemalhosseini Mojarad E, Kuppen PJ, Aghdaei HA, Zali MR (2013). "The CpG island methylator phenotype (CIMP) in colorectal ... strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island". ...
CpG island Law J, Jacobsen SE (2010). "Establishing, maintaining and modifying DNA methylation patterns in plants and animals ... In adult somatic tissues, cytosine residues may be methylated, and this occurs almost exclusively within a symmetric CpG ... Methylated C residues spontaneously deaminate to form T residues; hence CpG dinucleotides steadily mutate to TpG dinucleotides ... which gives rise to the under-representation of CpG dinucleotides in the human genome (they occur at only 21% of the expected ...
Her work initially as a postdoctoral research fellow twenty years ago identified the concept of CpG island methylator phenotype ... or CpG island hypermethylation in colorectal cancer. This concept of CIMP now is known to have implications for prognosis as ... "CpG island methylator phenotype in colorectal cancer". Proc. Natl. Acad. Sci. U.S.A. 96: 8681-6. doi:10.1073/pnas.96.15.8681. ...
... has one CpG island within the promoter. SMIM15 has lower levels of H3K4Me1 but higher levels of H3K4Me3 and H3K27Ac ...
In mammalian cells, clusters of CpG at the 5' ends of genes are termed CpG islands. 1% of all mammalian DNA is 5mC. While ... CpG islands overlapping gene promoters are de novo methylated resulting in aberrant inactivation of genes normally associated ... Bird, Adrian P. (May 1986). "CpG-rich islands and the function of DNA methylation". Nature. 321 (6067): 209-213. Bibcode: ... There are reports of age estimators with the methylation state of only one CpG in the gene ELOVL2. Estimation of age allows for ...
October 2013). "The CpG island methylator phenotype: what's in a name?". review. Cancer Research. 73 (19): 5858-68. doi:10.1158 ... Curtin K, Slattery ML, Samowitz WS (April 2011). "CpG island methylation in colorectal cancer: past, present and future". ...
Blackledge NP, Zhou JC, Tolstorukov MY, Farcas AM, Park PJ, Klose RJ (Apr 2010). "CpG islands recruit a histone H3 lysine 36 ... This mechanism acts to create a chromatin environment at CpG islands that highlights these regulatory elements and ... within FBXL11/KDM2A has the capacity to interact with non-methylated DNA and this domain targets FBXL11/KDM2A to CpG island ...
January 2006). "De novo CpG island methylation in human cancer cells". Cancer Research. 66 (2): 682-92. doi:10.1158/0008-5472. ... DNMT3a prefers CpG methylation to CpA, CpT, and CpC methylation, though there appears to be some sequence preference of ... DNMT3a methylates CpG sites at a rate much slower than DNMT1, but greater than DNMT3b. DNMT3L contains DNA methyltransferase ... The recognition motif for the human enzyme involves only three of the bases in the CpG dinucleotide pair: a C on one strand and ...
Regions in which cytosines prior to guanines are clustered and highly unmethylated are called CpG islands, and often serve as ... PRC2 is recruited by many elements, including CpG islands. PRC1, meanwhile, ubiquitinates H2AK119 using Ring1A/B's E3 ligase ... DNA methylation in humans and most other mammals refers to the methylation of a CpG. Methylation of these cytosines are common ...
In particular, he has focused on understanding how DNA encoded regulatory elements in vertebrates, called CpG islands, help to ... CS1 maint: discouraged parameter (link) Klose, Rob (2010). "CpG islands recruit a histone H3 lysine 36 demethylase". Mol. Cell ... Klose, Rob (2013). "ZF-CxxC domain-containing proteins, CpG islands and the chromatin connection". Biochem Soc Trans. 41 (3): ... Sir Adrian Bird at the Wellcome Centre for Cell Biology at the University of Edinburgh, Scotland, he studied the methyl CpG ...
Blackledge NP, Zhou JC, Tolstorukov MY, Farcas AM, Park PJ, Klose RJ (Apr 2010). "CpG islands recruit a histone H3 lysine 36 ... In many eukaryotes, the KDM2A protein contains a CXXC zinc finger domain capable of binding unmethylated CpG islands. It is ...
His research focuses on understanding DNA methylation and CpG islands, and their role in diseases such as Rett syndrome. Bird ... Bird's research has focused on CpG islands and their associated binding-factor MeCP2. He led the team which first identified ... Bird, A. P. (1986). "CpG-rich islands and the function of DNA methylation". Nature. 321 (6067): 209-13. Bibcode:1986Natur.321.. ... CpG islands-originally named "HpaII tiny fragments"-in vertebrate genomes. These are short genomic regions with a high density ...
Curtin, Karen; Slattery, Martha L; Samowitz, Wade S (2011). "CpG Island Methylation in Colorectal Cancer: Past, Present and ... CpG island methylator phenotype (CIMP) and BRAF mutation frequency from the database analyses of over 1,400 colorectal cancer ... "The CpG Island Methylator Phenotype: What's in a Name?". Cancer Research. 73 (19): 5858-68. doi:10.1158/0008-5472.CAN-12-4306. ...
This gene maps to a GC-rich region of the X chromosome and was identified by its proximity to a CpG island. It is thought to be ... Alcalay M, Toniolo D (1988). "CpG islands of the X chromosome are gene associated". Nucleic Acids Res. 16 (20): 9527-43. doi: ...
Jair KW, Bachman KE, Suzuki H, Ting AH, Rhee I, Yen RW, Baylin SB, Schuebel KE (January 2006). "De novo CpG island methylation ... DNA (cytosine-5)-methyltransferase 1 is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in ...
Cross SH, Charlton JA, Nan X, Bird AP (1994). "Purification of CpG islands using a methylated DNA binding column". Nat. Genet. ...
"Isolation of estrogen-responsive genes with a CpG island library". Mol Cell Biol. 18 (1): 442-9. doi:10.1128/mcb.18.1.442. PMC ...
Cross SH, Charlton JA, Nan X, Bird AP (1994). "Purification of CpG islands using a methylated DNA binding column". Nat. Genet. ...
Aïssani B, Bernardi G (October 1991). "CpG islands, genes and isochores in the genomes of vertebrates". Gene. 106 (2): 185-95. ...
Cross SH, Charlton JA, Nan X, Bird AP (March 1994). "Purification of CpG islands using a methylated DNA binding column". Nature ...
"Purification of CpG islands using a methylated DNA binding column". Nat. Genet. 6 (3): 236-44. doi:10.1038/ng0394-236. PMID ...
Cross SH, Charlton JA, Nan X, Bird AP (Mar 1994). "Purification of CpG islands using a methylated DNA binding column". Nature ...
CpG islands[edit]. In mammals, the only exception for this global CpG depletion resides in a specific category of GC- and CpG- ... Reciprocally, around 60-70% of human genes have a CpG island in their promoter region.[21][22] The majority of CpG islands are ... In mouse and human, around 60-70% of genes have a CpG island in their promoter region and most of these CpG islands remain ... rich sequences termed CpG islands that are generally unmethylated and therefore retained the expected CpG content.[19] CpG ...
The Kuomintang had no choice but to leave mainland China and relocate to the island of Taiwan in 1945 from Japan, then fled ... Office for Safeguarding National Security of the CPG in the HKSAR. *Urban Management (chengguan) ...
2010). "Human testis-specific PDHA2 gene: methylation status of a CpG island in the open reading frame correlates with ...
A cluster of CpG dinucleotides clustered together is called a CpG island, and in mammals, these CpG islands are one of the ... Methylation of CpG dinucleotides and/or islands within gene promoters is associated with transcriptional repression via ... Hypothetically, global hypomethylation should be associated with global increases in transcription, since CpG islands are most ... a CpG transformation technique which is sensitive to CpG methylation status, in which global hypomethylation has been observed. ...
CpG sites are frequently mutated and become rare in the genome, except at CpG islands where they remain unmethylated. ... Transcription from methylated CpG islands is strongly and heritably repressed.[69] Other miRNAs are epigenetically regulated by ... About 50% of miRNA genes are associated with CpG islands,[64] that may be repressed by epigenetic methylation. ... "Role of nucleosomal occupancy in the epigenetic silencing of the MLH1 CpG island". Cancer Cell. 12 (5): 432-44. PMC 4657456 . ...
This method leverages the tendency of methylated cytosines to cluster at CpG islands (CGIs) to enrich for areas of the genome ... of CpG sites in the entire genome.[34] In single cells, 40% of the CpG sites from the bulk sample are detected. To increase ... When RRBS is applied to bulk samples, majority of the CpG sites in gene promoters are detected, but site in gene promoters only ... In a sample of 20 pooled single cells, 63% of the CpG sites from the bulk sample were detected. Pooling single cells is one ...
Strand Breaks Can Initiate Gene Silencing and SIRT1-Dependent Onset of DNA Methylation in an Exogenous Promoter CpG Island". ...
CpG islands (or CG islands) are regions with a high frequency of CpG sites. Though objective definitions for CpG islands are ... "CpG island shores") rather than in the islands themselves.[12]. CpG islands typically occur at or near the transcription start ... CpG islands[edit]. How methylation of CpG sites followed by spontaneous deamination leads to a lack of CpG sites in methylated ... Unlike CpG sites in the coding region of a gene, in most instances the CpG sites in the CpG islands of promoters are ...
hypomethylation of CpG island. • positive regulation of peptidyl-serine phosphorylation. • platelet activation. • Fc-epsilon ...
... strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island". ...
Graff JR, Gabrielson E, Fujii H, Baylin SB, Herman JG (January 2000). "Methylation patterns of the E-cadherin 5' CpG island are ... The methylation patterns of the E-cadherin 5' CpG island are not stable. During metastatic progression of many cases of ...
... strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island»։ ...
... alterations in cancers that change gene expression levels include direct hypermethylation or hypomethylation of CpG islands of ...
Aïssani B, Bernardi G (1991). "CpG islands, genes and isochores in the genomes of vertebrates". Gene 106 (2): 185-95. PMID ...
Jan 2000). "Methylation patterns of the E-cadherin 5' CpG island are unstable and reflect the dynamic, heterogeneous loss of E- ... Os patróns de metilación da illa 5' CpG da E-cadherina non son estables. Durante a progresión da metástase de moitos casos de ...
"R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters". Molecular Cell. 45 (6): 814-25. ...
Distal promoters also frequently contain CpG islands, such as the promoter of the DNA repair gene ERCC1, where the CpG island- ... contain a CpG island.[27][28] CpG islands are generally 200 to 2000 base pairs long, have a C:G base pair content ,50%, and ... The presence of multiple methylated CpG sites in CpG islands of promoters causes stable silencing of genes.[30] Silencing of a ... but this is often followed by methylation of CpG sites in the promoter CpG island to cause the stable silencing of the gene.[30 ...
Two PCRs are then carried out on the modified DNA, using primer sets identical except at any CpG islands within the primer ... a novel PCR assay for methylation status of CpG islands". Proc Natl Acad Sci USA. 93 (13): 9821-9826. Bibcode:1996PNAS... ... and is used to detect methylation of CpG islands in genomic DNA. DNA is first treated with sodium bisulfite, which converts ...
600 to 800 somatically heritable heavily methylated CpG islands in promoters of genes in the tumors while these CpG islands are ... CpG islands keep their overall un-methylated state (or methylated state) extremely stably through multiple cell generations.[62 ... "Orphan CpG islands identify numerous conserved promoters in the mammalian genome". PLoS Genet. 6 (9): e1001134. doi:10.1371/ ... caused by somatically heritable promoter hypermethylation of CpG islands) than by mutations. As Vogelstein et al. point out, in ...
Epimutations include methylations or demethylations of the CpG islands of the promoter regions of genes, which result in ... strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island". ...
... the majority of gene promoters contain a CpG island with numerous CpG sites.[4] When many of a gene's promoter CpG sites are ... For example, in colorectal cancers about 600 to 800 genes are transcriptionally silenced by CpG island methylation (see ... "CpG islands" when densely clustered). Analysis of the pattern of methylation in a given region of DNA (which can be a promoter ... more than 18,000 CpG sites (of the roughly 450,000 analyzed CpG sites in the genome) had frequently altered methylation among ...
Ionian Islands (Corfu, Ithaca, Kefalonia, Kythira, Lefkada, Paxi, Zakynthos). *Macedonia (Chalkidiki, Drama, Florina, Grevena, ... cpg. - Cappadocian Greek. gmy. - Mycenaean Greek. pnt. - Pontic. tsd. - Tsakonian. yej. - Yevanic. ... North Aegean islands (Chios, Ikaria, Lemnos, Lesbos, Samos). *Peloponnese (Arcadia, Argolis, Corinthia, Laconia, Messenia, ... Central Greece (Aetolia-Acarnania (Aetolia, Acarnania), Attica, Boeotia, Euboea, Evrytania, Phocis, Phthiotis, Saronic Islands) ...
1949 (of CPG). 1954 (of PRC) Wang Yi. 王毅. State Councilor and Minister of Foreign Affairs CPC General Secretary Xi Jinping ( ... 1949 (of CPG) Fu Zhenghua. 傅政华. Minister of Justice CPC Guo Shengkun (Secretary of the CPC Central Political and Legal Affairs ... 1949 (of CPG). 1954 (of PRC) Police Commissioner-General [zh]. Zhao Kezhi. 赵克志. State Councilor and Minister of Public Security ... 1949 (of CPG). 1954 (of PRC) E Jingping. 鄂竟平. Minister of Water Resources CPC Vice-Premier Hu Chunhua ...
... the majority of gene promoters contain a CpG island with numerous CpG sites.[16] When many of a gene's promoter CpG sites are ... For example, in colorectal cancers about 600 to 800 genes are transcriptionally inhibited by CpG island methylation (see ... "A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters". Proceedings ...
"Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II ... strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island". ...
Cross SH, Charlton JA, Nan X, Bird AP (1994). "Purification of CpG islands using a methylated DNA binding column.". Nat. Genet. ...
"The nucleotide sequence of a CpG island demonstrates the presence of the first exon of the gene encoding the human lysosomal ...
"Hypomethylation of CD30 CpG islands with aberrant JunB expression drives CD30 induction in Hodgkin lymphoma and anaplastic ...
"A Genome-Wide Screen for Normally Methylated Human CpG Islands That Can Identify Novel Imprinted Genes". Genome Research. 12 (4 ...
... volume examines bioinformatic and molecular biological methods useful to identify and to explore the functions of CpG islands, ... Prediction of CpG Islands as an Intrinsic Clustering Property Found in Many Eukaryotic DNA Sequences and Its Relation to DNA ... Authoritative and practical, CpG Islands: Methods and Protocols aims to provide readers with the information and methodologies ... Methods for the Measurement of DNA Methylation at CpG Islands. * Front Matter Pages 81-81 ...
G/C boxes were found to be rare in CpG-depleted DNA and plentiful in CpG islands, where they occurred in 3 CpG islands, as ... Two theories for the maintenance of a high frequency of CpG dinucleotides in CpG islands were tested: that CpG islands in ... CpG islands, separated by several thousand base-pairs of CpG-depleted DNA. The 5 CpG islands extended through 5-flanking DNA ... In this study, a large number of sequences of vertebrate genes were screened for the presence of CpG islands. Each CpG island ...
... called CpG island methylator prototype, or CIMP. Higher levels of CpG island hypermethylation are found in CIMP. The frequent ... the CpG island is hypomethylated, and the rest of the genome is methylated. It is evident that the hypomethylation of the CpG ... A CpG island is a Cytosine and Guanine linked by a phosphate in a repeated sequence. These are genetic hotspots as they are ... Hypermethylated CpG islands also act as biomarkers, as they can help distinguish cancer from normal cells in the same sample. ...
CpG Islands (Islands < 300 Bases are Light Green) (. CpG Islands). This track is part of a parent called CpG Islands. To show ... The CpG count is the number of CG dinucleotides in the island. The Percentage CpG is the ratio of CpG nucleotide bases (twice ... CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near ... CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole. ...
CpG islands are short, dispersed regions of unmethylated DNA with a high frequency of CpG dinucleotides relative to the bulk ... CpG islands as gene markers in the human genome.. Larsen F1, Gundersen G, Lopez R, Prydz H. ... We have analyzed 375 genes and 58 pseudogenes from the human entries in the EMBL Database for the presence of CpG islands. All ... More than half of the genes analyzed were associated with islands. All housekeeping and widely expressed genes have a CpG ...
Combining the number of CpG islands with the proportion of island-associated genes, we estimate that the total number of genes ... Number of CpG islands and genes in human and mouse. F Antequera and A Bird ... Analysis of a selection of genes suggests that both human and mouse are losing CpG islands over evolutionary time due to de ... Our results suggest that there are approximately 45,000 CpG islands per haploid genome in humans and 37,000 in the mouse. ...
CpG islands are usually unmethylated in a genome, especially in the promoter regions [2], in contrast, ~80% of CpG ... There has been much interest in CpG islands (CGIs), clusters of CpG dinucleotides in GC-rich regions, because they are ... F. Antequera and A. P. Bird, "Number of CpG islands and genes in human and mouse," Proceedings of the National Academy of ... CpG islands in this table were identified by Takai and Jones algorithm [7]. The number of genes in each fish genome was based ...
CpG Islands CpG Islands (Islands < 300 Bases are Light Green) hide. dense. squish. pack. full. Unmasked CpG CpG Islands on All ... The CpG count is the number of CG dinucleotides in the island. The Percentage CpG is the ratio of CpG nucleotide bases (twice ... CpG islands are associated with genes, particularly housekeeping genes, in vertebrates. CpG islands are typically common near ... CpG Islands (Islands < 300 Bases are Light Green) Tracks (. All Regulation tracks). Display mode: hide. show. All. ...
Methylated CpG dinucleotides at position 5 of cytosine are associated with transcriptional repression and an inactive chromatin ... Figure 3. Chromatin structure of CpG islands. The distribution of methylated and nonmethylated CpG dinucleotides is shown at ... 2010) CpG islands influence chromatin structure via the CpG‐binding protein Cfp1. Nature 464: 1082-1086. ... genes are associated with CpG islands, as is clearly shown by the high density of CpG dinucleotides around their 5′ ends. In ...
CpG island, DNA hypermethylation and restored GSTP1 expression. Using a PCR assay, somatic GSTP1 ,CpG island, DNA ... GSTP1 CpG island DNA hypermethylation in hepatocellular carcinomas Int J Oncol. 2000 Apr;16(4):663-76. doi: 10.3892/ijo.16.4. ... GSTP1 ,CpG island, DNA hypermethylation in HCC DNA was assessed by Southern blot analysis, via a polymerase chain reaction (PCR ... The data indicate that GSTP1 ,CpG island, DNA hypermethylation changes appear frequently in human HCC. In addition, the data ...
... mechanism for carcinogenesis in colorectal carcinomas and adenomas characterized by methylation of multiple CpG islands. The ... The CpG island methylator phenotype (CIMP) is a newly described ... Concordant CpG island methylation in hyperplastic polyposis Am ... The CpG island methylator phenotype (CIMP) is a newly described mechanism for carcinogenesis in colorectal carcinomas and ... Our findings of concordant CpG island methylation of HPs in multiple/large HPs or hyperplastic polyposis supports the concept ...
... which can rapidly assess the methylation status of virtually any group of CpG sites within a CpG island, independent of the use ... Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. J G Herman, J R Graff, S Myöhänen, B D ... MSP requires only small quantities of DNA, is sensitive to 0.1% methylated alleles of a given CpG island locus, and can be ... Precise mapping of DNA methylation patterns in CpG islands has become essential for understanding diverse biological processes ...
Functional Relevance of CpG Island Length for Regulation of Gene Expression Message Subject (Your Name) has forwarded a page to ... Functional Relevance of CpG Island Length for Regulation of Gene Expression. Navin Elango and Soojin V. Yi ... Functional Relevance of CpG Island Length for Regulation of Gene Expression. Navin Elango and Soojin V. Yi ... Functional Relevance of CpG Island Length for Regulation of Gene Expression. Navin Elango and Soojin V. Yi ...
To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal ... The CpG island methylation phenotype (CIMP), characterized by the extensive hypermethylation of multiple gene CpG islands, was ... "CpG island methylator phenotype-low (CIMP-low) colorectal cancer shows not only few methylated CIMP-high-specific CpG islands, ... "CpG island methylator phenotype in colorectal cancers: comparison of the new and classic CPG island methylator phenotype marker ...
this methylation at CpG islands thats found in cancer.. So this is, tends to be called CpG island hypermethylation, or CGI ... CPG island, so you dont see methylation in general at CPG islands. ... 7.2 Hypermethylation of CpG islands in cancer. To view this video please enable JavaScript, and consider upgrading to a web ... CpG island spread throughout the genome in general are hypomethylated.. And so whats unusual to find is one thats ...
2) ⇓ . The CpG island at MGMT was methylated in a single case of the primary prostate cancers (1%; Fig. 2C ⇓ ). CpG islands at ... In this study, by using a Kaplan-Meier analysis, we found that of all of the CpG islands tested, only PTGS2 CpG island ... A, NIM at 16 CpG islands for normal prostate tissues taken from 13 transplant tissue donors. B, NIM at 16 CpG islands for tumor ... For instance, hypermethylation at the GSTP1 CpG island in combination with hypermethylation at the MDR1 CpG island yields a ...
The effect of CpG islands on transgene expression was first tested in cultured cells. In transient transfection it was ... Transgenic mice were used to study the effect of CpG islands on the level and pattern of transgene expression in vivo. ... Even when integrated into the genome of cultured cells, CpG islands are not able to confer position-independent, copy number- ... However, the results from bulk analysis of primary clones suggest that CpG islands improve the level of expression in cultured ...
Abstract 5004: CpG island methylator phenotype in bladder cancer. Woonbok Chung, Jolanta Bondaruk, Nianxiang Zhang, Jaroslav ... Abstract 5004: CpG island methylator phenotype in bladder cancer. Woonbok Chung, Jolanta Bondaruk, Nianxiang Zhang, Jaroslav ... Abstract 5004: CpG island methylator phenotype in bladder cancer. Woonbok Chung, Jolanta Bondaruk, Nianxiang Zhang, Jaroslav ... Abstract 5004: CpG island methylator phenotype in bladder cancer Message Subject (Your Name) has forwarded a page to you from ...
C in CpG islands that were methylated remains unaffected. Asterisks show two CpG islands not methylated. ... CpG Island Methylation in Sporadic and Neurofibromatis Type 2-Associated Schwannomas. Pilar Gonzalez-Gomez, M. Josefa Bello, M ... CpG Island Methylation in Sporadic and Neurofibromatis Type 2-Associated Schwannomas. Pilar Gonzalez-Gomez, M. Josefa Bello, M ... CpG Island Methylation in Sporadic and Neurofibromatis Type 2-Associated Schwannomas. Pilar Gonzalez-Gomez, M. Josefa Bello, M ...
I use CpG Island Explorer to predicate CpG islands,but in one gene I did not get CpG island in the promoter region adjacent to ... I only get one CpG island about 4kb upstream the ATG codon, does the CpG region could be representative for study? If it is not ... Can these CpG islands be representative? - (Jul/11/2005 ). I get the DNA sequence 5kb upstream from exon1 and exon1 to ... If the CpG island is far away from the promoter or transcriptional start site, it is hard to say whether its methylation has ...
Virus-like attachment sites and plastic CpG islands:landmarks of diversity in plant Del retrotransposons.. [Guilherme M Q Cruz ... While some features are common to all Del elements, CpG island patterns within the LTRs were particular to lineage specific ...
CpG island coordinates CGIs genomic coordinates were obtained from the UCSC GB CpgIslandExt track. In this track CpG islands ... To estimate the methylation of each CpG island we calculated the mean of all CpGs methylation values into a CpG island. We were ... Additionally, by analyzing SNP frequency in CpG islands, we demonstrated that CpG islands in regions under selective pressure ... Additionally, by analyzing SNP frequency in CpG islands, we demonstrated that CpG islands in regions under selective pressure ...
... John P. Thomson,1,* Peter J. Skene,1,* Jim ... CpG islands (CGIs) are prominent in the mammalian genome owing to their GC-rich base composition and high density of CpG ... A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol. 2008;6:e22. [PMC free ... Sp1 sites in the mouse aprt gene promoter are required to prevent methylation of the CpG island. Genes Dev. 1994;8:2282-2292. [ ...
CpG island 8641. Synonyms: CGI8641. Gene nomenclature, locus information, and GO, OMIM, and PMID associations are updated daily ...
CpG island 899. Synonyms: CGI899. Gene nomenclature, locus information, and GO, OMIM, and PMID associations are updated daily ...
CpG island 8613. Synonyms: CGI8613. Gene nomenclature, locus information, and GO, OMIM, and PMID associations are updated daily ...
... and widespread hypermethylation of CpG islands, especially in the promoters of genes, referred to as the CpG island methylator ... Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer. J Natl Cancer Inst 2006;98: ... CpG island methylator phenotype in colorectal cancer. Proc Natl Acad Sci U S A 1999;96:8681-6. ... Ethnicity and Risk for Colorectal Cancers Showing Somatic BRAF V600E Mutation or CpG Island Methylator Phenotype. Dallas R. ...
... in a setting of widespread promoter CpG island methylation called the CpG island methylator phenotype (CIMP; refs. 26-28). A ... CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut 2009;58:90 ... CpG island methylator phenotype-low (CIMP-low) in colorectal cancer: possible associations with male sex and KRAS mutations. J ... The CpG island methylator phenotype in colorectal cancer. J Mol Diagn 2007;9:281-3. ...
... of all genes in the human genome is overlapped by a CpG island (CGI). CGIs have known functions in the transcription initiation ... Hackenberg M, Barturen G, Carpena P et al (2010) Prediction of CpG-island function: CpG clustering vs. sliding-window methods. ... CpG islands Clustering DNA words DNA methylation Virtual machine This is a preview of subscription content, log in to check ... Gardiner-Garden M, Frommer M (1987) CpG islands in vertebrate genomes. J Mol Biol 196:261-282CrossRefPubMedGoogle Scholar ...
Six sequences were found to be homologous to known genes having one or more 5′-CpG island(s) (5′-CGI). Of these, acyl-CoA ... Correction: Relation of DNA Methylation of 5′-CpG Island of ACSL3 to Transplacental Exposure to Airborne Polycyclic Aromatic ...
  • The CpG island methylator phenotype (CIMP) is a newly described mechanism for carcinogenesis in colorectal carcinomas and adenomas characterized by methylation of multiple CpG islands. (nih.gov)
  • To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal cancer (CRC) in Northeast China. (hindawi.com)
  • Colorectal cancers arising from serrated polyps are characterized by the CpG island methylator phenotype (CIMP) and somatic mutation (V600E) in the BRAF proto-oncogene. (aacrjournals.org)
  • PTGS2 (COX-2) expression in colon cancer has been inversely associated with survival as well as tumoral microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). (aacrjournals.org)
  • The CpG island methylator phenotype (CIMP), characterised by widespread promoter methylation, is associated with microsatellite instability (MSI) and BRAF mutation in colorectal cancer. (bmj.com)
  • Aims CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation, and the cell-cycle regulatory proteins often change in human neoplasms. (bmj.com)
  • CpG island methylator phenotype (CIMP) is a unique epigenetic phenomenon observed in cancer. (grantome.com)
  • CpG island methylator phenotype association with upregulated telomerase activity in hepatocellular carcinoma. (semanticscholar.org)
  • CpG island methylator phenotype (CIMP) involves the targeting of multiple genes by promoter hypermethylation. (semanticscholar.org)
  • We hypothesized that cellular DNMT3B level might influence the occurrence of widespread CpG island methylation (i.e., the CpG island methylator phenotype, CIMP) in colon cancer. (umn.edu)
  • Background CpG island methylator phenotype (CIMP) has been identified as a distinct molecular subtype of gastric cancer, yet associations with survival are conflicting. (cf.ac.uk)
  • There has been much interest in CpG islands (CGIs), clusters of CpG dinucleotides in GC-rich regions, because they are considered gene markers and involved in gene regulation. (hindawi.com)
  • CGIs are clusters of CpG dinucleotides in GC-rich regions, usually ~1 kb long [ 1 ]. (hindawi.com)
  • The mutation rate of the methylated CpG (5mCpG) to TpG was estimated to be ~10-50-folds higher than that of the unmethylated CpG site due to a high rate of deamination at the 5mCpG, which subsequently leads to an overall loss of CpG dinucleotides and a potential loss of CGIs [ 4 , 5 ]. (hindawi.com)
  • 6 ] found an association of DNA methylation in CpG-poor promoters in the germline with an increased loss of CpG dinucleotides, implying that characteristics of the CGIs have been weakened or even vanished in the course of evolution. (hindawi.com)
  • Those studies revealed that the mouse has undergone a faster CpG loss than the human, thus, has fewer CGIs and weaker CGI characteristics. (hindawi.com)
  • CGIs represent approximately 1% of the genome, and the large majority of them remain nonmethylated despite their high density of CpG dinucleotides. (els.net)
  • DNA methylation at CpG islands (CGIs) is one of the most intensively studied epigenetic mechanisms. (pubmedcentralcanada.ca)
  • These CGIs are enriched at genes, about 60% of all genes in the human genome containing a CpG island upstream [2] . (pubmedcentralcanada.ca)
  • CpG islands (CGIs) are prominent in the mammalian genome owing to their GC-rich base composition and high density of CpG dinucleotides 1 , 2 . (pubmedcentralcanada.ca)
  • The data indicate that a primary function of non-methylated CGIs is to genetically influence the local chromatin modification state by interaction with Cfp1 and perhaps other CpG-binding proteins. (pubmedcentralcanada.ca)
  • To characterize the chromatin modifications typical of CGIs, we used the methyl-CpG-sensitive restriction endonuclease HinPI (cleavage site GCGC) to release small chromatin fragments from purified brain nuclei, as described previously 9 . (pubmedcentralcanada.ca)
  • CGIs have known functions in the transcription initiation and outstanding compositional features like high G+C content and CpG ratios when compared to the bulk DNA. (springer.com)
  • In addition, we illustrate how to easily cross the output of a CpG island prediction algorithm with our methylation database to detect differentially methylated CGIs. (springer.com)
  • CpG islands (CGIs) are associated with most mammalian gene promoters. (elifesciences.org)
  • CpG islands (CGIs) function as promoters for approximately 60% of human genes. (fpwr.org)
  • Hypomethylated, CpG-rich DNA segments (CpG islands, CGIs) are epigenome markers involved in key biological processes. (ugr.es)
  • In particular, histone modifications in CpG islands (CGIs) are associated with different chromatin states and with transcription activity. (biomedcentral.com)
  • We have characterized the regions of H3K9me2 nucleation, with our analysis revealing that H3K9me2 is nucleated in HSPCs at CpG islands (CGIs) and CGI-like sequences across the genome. (biomedcentral.com)
  • Aberrant DNA methylation is induced at specific promoter CpG islands (CGIs) in contrast with mutations. (diagenode.com)
  • The human genome contains ∼30,000 CpG islands (CGIs). (ox.ac.uk)
  • CpG islands (CGIs) are interspersed DNA sequences that have unusually high CpG ratios and GC contents. (biomedcentral.com)
  • Despite their involvement in the regulation of gene expression and their importance as genomic markers for promoter prediction, no objective standard exists for defining CpG islands (CGIs), since all current approaches rely on a large parameter space formed by the thresholds of length, CpG fraction and G+C content. (ugr.es)
  • Given the higher frequency of CpG dinucleotides at CGIs, as compared to bulk DNA, the distance distributions between neighboring CpGs should differ for bulk and island CpGs. (ugr.es)
  • CpGcluster's CGIs overlapping with the Transcription Start Site (TSS) show the highest statistical significance, as compared to the islands in other genome locations, thus qualifying CpGcluster as a valuable tool in discriminating functional CGIs from the remaining islands in the bulk genome. (ugr.es)
  • Another outstanding feature is that all predicted CGIs start and end with a CpG dinucleotide, which should be appropriate for a genomic feature whose functionality is based precisely on CpG dinucleotides. (ugr.es)
  • Regions known as CpG islands (CGIs), which are refractory to DNA methylation, are often associated with gene promoters and play central roles in gene regulation. (cam.ac.uk)
  • In this study, we generated whole genome bisulfite sequencing (WGBS) data with high sequencing depth in induced pluripotent stem cell (iPSC) and neuronal progentior cell (NPC), and investigated the relationship between DNA methylation changes in CpG islands (CGIs) and corresponding gene expression during NPC differentiation. (yonsei.ac.kr)
  • CpG islands (CGIs) are very important and useful, as they carry functionally relevant epigenetic loci for whole genome studies. (ac.ir)
  • Chromosome 25 had the largest number of CGIs (4556) and the highest CGI density (106.20 CGIs/Mb).A significant positive correlation observed among CGI densities with guanine-cytosine (GC) content, Obs CpG /Exp CpG , recombination rate and gene density. (ac.ir)
  • The remaining CpGs are clustered in regions referred to as CpG islands (CGIs). (ac.ir)
  • Aberrant DNA methylation of CpG islands (CGIs) is a common alteration during malignant transformation that leads to the abnormal silencing of tumor suppressor genes and plays a role in disease initiation and progression. (academic2.ru)
  • Furthermore, the molecular mechanisms controlling the methylation status of CpG islands in normal and malignant cells were analyzed and factors were identified that are responsible for maintaining or establishing methylated states of CGIs in health and disease as well as for de novo methylation in cancer. (academic2.ru)
  • Our findings of concordant CpG island methylation of HPs in multiple/large HPs or hyperplastic polyposis supports the concept that some patients have a hypermethylator phenotype characterized by methylation of multiple HPs and other colorectal lesions. (nih.gov)
  • CpG island methylation phenotype (CIMP), characterized by the extensive hypermethylation of multiple CpG islands, is currently recognized as one of the major mechanisms in the colorectal carcinogenesis [ 7 , 8 ]. (hindawi.com)
  • DNA hypermethylation is a common epigenetic abnormality in cancer, and some cancers are characterized by the presence of intense hypermethylation at multiple loci, termed CpG island methylation phenotype (CIMP). (aacrjournals.org)
  • 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. (els.net)
  • Antequera F (2003) Structure, function and evolution of CpG islands promoters. (els.net)
  • islands are found, they're in the promoters of tumour suppressor genes. (coursera.org)
  • The results suggest that full size CpG islands used as promoters do not necessarily overcome the negative effects of neighbouring chromatin to give ubiquitous transgene expression independent of the integration site. (bl.uk)
  • In prior work, we analyzed CpG island methylation levels within gene promoters (nᅠ=ᅠ16,421) in leukocytes collected from mothers and their infants from a pregnancy cohort in Durham County, North Carolina. (rice.edu)
  • ZBTB 2 preferentially binds to CpG island promoters, where it acts as a transcriptional activator. (embopress.org)
  • ZBTB 2 is a novel reader of unmethylated DNA in mouse embryonic stem cells, and regulates cellular differentiation as an activator at CpG island promoters. (embopress.org)
  • ZBTB 2 preferentially binds to unmethylated CpG island promoters. (embopress.org)
  • Although hypermethylation of the INK4a and INK4b promoters is frequently involved in murine lymphomas, the p19 ARF CpG island is infrequently methylated in the murine primary lymphomas studied in this work. (oup.com)
  • In mammalian genomes, CpG islands are typically 300-3,000 base pairs in length, and have been found in or near approximately 40% of promoters of mammalian genes. (wikipedia.org)
  • [9] About 70% of human promoters have a high CpG content. (wikipedia.org)
  • Unlike CpG sites in the coding region of a gene, in most instances the CpG sites in the CpG islands of promoters are unmethylated if the genes are expressed. (wikipedia.org)
  • In humans, about 70% of promoters located near the transcription start site of a gene (proximal promoters) contain a CpG island. (wikipedia.org)
  • Over 60% of human genes and almost all house-keeping genes have their promoters embedded in CpG islands. (wikipedia.org)
  • Although vertebrate DNA is generally depleted in the dinucleotide CpG, it has recently been shown that some vertebrate genes contain CpG islands, regions of DNA with a high G+C content and a high frequency of CpG dinucleotides relative to the bulk genome. (nih.gov)
  • CpG islands were predicted by searching the sequence one base at a time, scoring each dinucleotide (+17 for CG and -1 for others) and identifying maximally scoring segments. (ucsc.edu)
  • The reason for methylation to be almost exclusive to CpG dinucleotides is the symmetry of the dinucleotide. (wikipedia.org)
  • DNA methylation occurs naturally throughout the genome, mostly at positions where cytosine is bonded to guanine to form a CpG dinucleotide. (elifesciences.org)
  • The cytosine must be linked to guanine, with the guanine occurring at the 3 ′ ("three prime") end of the DNA molecule, in a formation that, in scientific notation , is expressed as 5 ′ -CG-3 ′ and is referred to as a CpG dinucleotide (with the "p" representing a phosphate group). (encyclopedia.com)
  • The frequency of occurrence of the CpG dinucleotide in the genome is not random, as would be expected. (encyclopedia.com)
  • Instead, the CpG dinucleotide is greatly under represented in eukaryotic genomes, occurring at approximately 5 to 10 percent of its predicted frequency, according to some estimates. (encyclopedia.com)
  • Finally, we show that this mutant PPM1D-induced NAMPT inhibitor sensitivity is driven by hypermethylation of CpG islands throughout the genome, and in particular, the epigenetic silencing of nicotinic acid phosphoribosyltransferase (NAPRT), a key gene involved in nicotinamide adenine dinucleotide (NAD) biosynthesis. (nature.com)
  • Unmethylated CpG dinucleotide sites can be detected by Toll-like receptor 9 [2] ( TLR 9 ) on plasmacytoid dendritic cells , monocytes, natural killer (NK) cells, and B cells in humans. (wikipedia.org)
  • CpG islands are characterized by CpG dinucleotide content of at least 60% of that which would be statistically expected (~4-6%), whereas the rest of the genome has much lower CpG frequency (~1%), a phenomenon called CG suppression . (wikipedia.org)
  • And this is called a CpG dinucleotide. (coursera.org)
  • CpG dinucleotide. (coursera.org)
  • Since CpG islands contain multiple CpG dinucleotide sequences, there appear to be more than 20 million CpG dinucleotides in the human genome. (wikipedia.org)
  • DNA methylation is a chemical modification that typically occurs within a CpG dinucleotide region in adult somatic cells ( 7 , 8 ). (spandidos-publications.com)
  • CpG islands in vertebrate genomes. (nih.gov)
  • Two theories for the maintenance of a high frequency of CpG dinucleotides in CpG islands were tested: that CpG islands in methylated genomes are maintained, despite a tendency for 5mCpG to mutate by deamination to TpG+CpA, by the structural stability of a high G+C content alone, and that CpG islands associated with exons result from some selective importance of the arginine codon CGX. (nih.gov)
  • Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes . (ucsc.edu)
  • CpG islands are usually unmethylated in a genome, especially in the promoter regions [ 2 ], in contrast, ~80% of CpG dinucleotides in the mammalian genomes are methylated [ 2 , 3 ]. (hindawi.com)
  • BACKGROUND: Majority of CpG dinucleotides in mammalian genomes tend to undergo DNA methylation, but most CpG islands are resistant to such epigenetic modification. (rti.org)
  • CpG dinucleotides are frequently methylated in vertebrate genomes. (biomedcentral.com)
  • High CpG methylation in mammalian genomes has an evolutionary cost because it increases the frequency of spontaneous mutations. (wikipedia.org)
  • CpG dinucleotides have long been observed to occur with a much lower frequency in the sequence of vertebrate genomes than would be expected due to random chance. (wikipedia.org)
  • The frequency of CpG dinucleotides in human genomes is 1%-less than one-quarter of the expected frequency. (wikipedia.org)
  • It was proposed that the CpG deficiency is due to an increased vulnerability of methylcytosines to spontaneously deaminate to thymine in genomes with CpG cytosine methylation. (wikipedia.org)
  • Many genes in mammalian genomes have CpG islands associated with the start of the gene [8] ( promoter regions ). (wikipedia.org)
  • Here we computed cleavage rates of all dinucleotides including the methylated CpG and unmethylated CpG dinucleotides using data of the Whole Genome Sequencing datasets of the 1000 Genomes project. (ist.ac.at)
  • CpG islands, which are clusters of CpG dinucleotides in GC-rich regions, are considered gene markers and represent an important feature of mammalian genomes. (biomedcentral.com)
  • To date, there seems to be no comparative analysis of CpG islands and their density at the DNA sequence level among mammalian genomes and of their correlations with other genome features. (biomedcentral.com)
  • In this study, we performed a systematic analysis of CpG islands in ten mammalian genomes. (biomedcentral.com)
  • We found that both the number of CpG islands and their density vary greatly among genomes, though many of these genomes encode similar numbers of genes. (biomedcentral.com)
  • Our study revealed that CpG islands vary greatly among mammalian genomes. (biomedcentral.com)
  • These findings should be useful for studying mammalian genomes, the role of CpG islands in gene function, and molecular evolution. (biomedcentral.com)
  • In order to understand the role of CpG island hypermethylation in cancer, it is useful to consider a particular tumor type, called CpG island methylator prototype, or CIMP. (wikipedia.org)
  • Higher levels of CpG island hypermethylation are found in CIMP. (wikipedia.org)
  • Tumors possessing a CIMP usually display concurrent hypermethylation of multiple promoter CpG islands. (grantome.com)
  • Tumor cells with relatively high levels of CpG island methylation are considered CpG island methylator phenotypes (CIMP). (beds.ac.uk)
  • A recent study [ 29 , 30 ] demonstrated reduced fidelity in replicating methylation patterns of CpG islands in CIMP gastric cell lines compared to non-CIMP lines, mostly caused by de novo methylation. (beds.ac.uk)
  • Methylation of promoter-associated CpG islands has been found to play an important role in gene silencing, genomic imprinting, X-chromosome inactivation, and carcinogenesis [ 7 , 8 ]. (hindawi.com)
  • By analyzing methylation data of 25 cell lines from the Encyclopedia of DNA Elements (ENCODE) Consortium, we compared the DNA methylation of CpG islands in genomic regions under selective pressure with the methylation of CpG islands in the remaining part of the genome. (pubmedcentralcanada.ca)
  • A part of all CpG sites present in the genome are clustered into CpG islands that are defined as genomic regions with increased CpG density. (pubmedcentralcanada.ca)
  • A 2002 study revised the rules of CpG island prediction to exclude other GC-rich genomic sequences such as Alu repeats . (wikipedia.org)
  • Restriction Landmark Genomic Scanning (RLGS) is a two-dimensional gel electrophoresis that assesses the methylation status of thousands of CpG islands. (northwestern.edu)
  • We identified a 600 bp region of the BRCA1 CpG island that possessed strong promoter activity (~40-fold above control), and determined the cytosine methylation patterns of the 30 CpG sites within this region by sodium bisulfite genomic sequencing. (elsevier.com)
  • CpG sites occur with high frequency in genomic regions called CpG islands (or CG islands). (wikipedia.org)
  • Predicting CpG Islands and Their Relationship with Genomic Feature in Cattle by Hidden Markov Model Algorithm', Iranian Journal of Applied Animal Science , 6(3), pp. 571-579. (ac.ir)
  • We observed significant correlations between CpG island density and genomic features such as number of chromosomes, chromosome size, and recombination rate. (biomedcentral.com)
  • Takai D, Jones PA (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. (springer.com)
  • In this study, a large number of sequences of vertebrate genes were screened for the presence of CpG islands. (nih.gov)
  • Neither of these theories could account for the distribution of CpG dinucleotides in the sequences analysed. (nih.gov)
  • To test whether non-methylated CpG-dense sequences are sufficient to establish domains of H3K4me3, we analysed artificial CpG clusters that were integrated into the mouse genome. (pubmedcentralcanada.ca)
  • Various embodiments of the invention described herein include methods for using single point genome signature tags to analyze the related families present in a sample, methods for analyzing sequences associated with hyper- and hypo-methylated CpG islands, methods for visualizing organismic complexity change in a sampling location over time and methods for generating the genome signature tag profile of a sample of fragmented DNA. (energy.gov)
  • Six sequences were found to be homologous to known genes having one or more 5′-CpG island(s) (5′-CGI). (ccceh.org)
  • In mammals, the only exception for this global CpG depletion resides in a specific category of GC- and CpG-rich sequences termed CpG islands that are generally unmethylated and therefore retained the expected CpG content. (wikipedia.org)
  • The CpG notation is used to distinguish this single-stranded linear sequence from the CG base-pairing of cytosine and guanine for double-stranded sequences. (wikipedia.org)
  • Given the frequency of GC two-nucleotide sequences, the number of CpG dinucleotides is much lower than would be expected. (wikipedia.org)
  • This was exemplified by young CpG rich lineage-restricted repeat sequences that evaded DNA methylation in the absence of co-evolved mechanisms targeting methylation to these sequences, and species specific DNA binding events that protected against DNA methylation in CpG poor regions. (cam.ac.uk)
  • There are 28,890 CpG islands in the human genome, (50,267 if one includes CpG islands in repeat sequences). (wikipedia.org)
  • 15 ] developed a new algorithm, namely CpGcluster, that entirely depends on the statistical significance of a CpG cluster from random sequences in the same chromosome. (biomedcentral.com)
  • The distribution of methylated and nonmethylated CpG dinucleotides is shown at the bottom (black or white circles, respectively). (els.net)
  • Approximately 80% of CpG dinucleotides are methylated in the 5′ position of cytosine in the mammalian genome. (els.net)
  • While the cytosine bases in most CpG dinucleotides are methylated, there are short stretches of DNA known as CpG islands that contain a high proportion of unmethylated CpG dinucleotides. (elifesciences.org)
  • The introduction of methylation-specific PCR and sodium bisulfite modification added tools to the belt of cancer epigenetics research, and the list of candidate genes with aberrant methylation of their CpG islands has been growing since. (wikipedia.org)
  • In tumor cells, aberrant methylation of CpG dinucleotides at the 5' end of tumor suppressor genes is frequently associated with gene silencing. (roche.com)
  • Effects of genome architecture and epigenetic factors on susceptibility of promoter CpG islands to aberrant DNA methylation induction. (diagenode.com)
  • Because a CpG island is found at the 5' end of the BRCA1 gene, we hypothesized that the decreased BRCA1 mRNA in sporadic breast cancer was associated with aberrant cytosine methylation of the CpG island. (elsevier.com)
  • These findings suggest that aberrant cytosine methylation of the BRCA1 CpG island promoter may be one mechanism of BRCA1 repression in sporadic breast cancer. (elsevier.com)
  • Rice, JC, Massey-Brown, KS & Futscher, BW 1998, ' Aberrant methylation of the BRCA1 CpG island promoter is associated with decreased BRCA1 mRNA in sporadic breast cancer cells ', Oncogene , vol. 17, no. 14, pp. 1807-1812. (elsevier.com)
  • Aberrant DNA methylation of promoter CpG islands is associated with transcriptionally repressive heterochromatin in neoplasia. (elsevier.com)
  • Thus, this study underscores the importance of detailed mapping of methylation patterns within a CpG island locus that may provide insights into the progressive nature of aberrant DNA methylation and its relationship with transcriptional silencing during the neoplastic process. (elsevier.com)
  • We have taken advantage of the fact that many mammalian genes are associated with CpG islands whose distinctive properties allow their physical separation from bulk DNA. (pnas.org)
  • The α‐globin and the aldose reductase (ADO) genes are associated with CpG islands, as is clearly shown by the high density of CpG dinucleotides around their 5′ ends. (els.net)
  • Methylated CpG dinucleotides at position 5 of cytosine are associated with transcriptional repression and an inactive chromatin conformation in mammals. (els.net)
  • The majority of CpG pairs in mammals are chemically modified by the covalent attachment of a methyl group to the C5 position of the cytosine ring. (wikipedia.org)
  • These complexes have an important role in the regulation of genes during early development in animals, but the mechanism by which PRC1 recognizes CpG islands in mammals has remained enigmatic. (elifesciences.org)
  • 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. (wikipedia.org)
  • In mammals, 70% to 80% of CpG cytosines are methylated. (wikipedia.org)
  • The DNA of most vertebrates, especially mammals, is depleted in CpG dinucleotides. (ac.ir)
  • Hypermethylation of CpG islands has been described in almost every type of tumor. (wikipedia.org)
  • The first discovery of methylation in a CpG island of a tumor suppressor gene in humans was that of the Retinoblastoma (Rb) gene in 1989. (wikipedia.org)
  • Cancer epigenetic silencing in its current state was born in the labs of Baylin and Jones, where it was proven that CpG island hypermethylation was a common inactivation mechanism of the tumor suppressor gene p16INK4a. (wikipedia.org)
  • The frequent hypermethylation of CpG islands in these tumors as well as their irregularity are ways to determine that hypermethylated CpGs differ by tumor type. (wikipedia.org)
  • 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. (pnas.org)
  • In cancer cells, several tumor suppressor genes such as p16 INK4a , VHL , hMLH1 , and BRCA1 have been found to have hypermethylation of normally unmethylated CpG islands within the promoter regions. (aacrjournals.org)
  • The promoter of INK4a resides within a CpG island, and abnormal, tumor-associated hypermethylation has been observed in many tumor types and found to result in silencing of the gene ( 14 , 39 ). (asm.org)
  • Dnmt3b can induce colon tumor in mice with methylation in specific CpG islands. (umn.edu)
  • The hypermethylation of promoter CpG islands affects tumor suppressive mRNAs ( 9 - 10 ). (spandidos-publications.com)
  • Hypermethylation of CpG islands is thought to contribute to carcinogenesis through the inactivation of tumor suppressor genes. (beds.ac.uk)
  • On the other hand, CpG islands are susceptible to hypermethylation, and when it occurs in the promoter, it is associated with gene silencing and can promote the deactivation of tumor suppressor genes. (beds.ac.uk)
  • Since DNA methylation can repress gene transcription at a distance (1 kb-2 kb) from the promoter region, we have investigated the methylation status of this BRCA1 CpG island. (roche.com)
  • CpG islands are differentially methylated in imprinted genes and in the inactive X chromosomes. (els.net)
  • P2 is located within a CpG island that is differentially methylated between males and females and overlaps conserved YY1 binding sites that are only bound on the inactive X chromosome where the sites are unmethylated. (biomedcentral.com)
  • These observations in the E6-expressing HMEC correlate well with the finding that CpG island methylation is a mechanism of p16 inactivation in the development of human tumors, including breast cancer. (asm.org)
  • This would imply that colorectal cancer will not necessarily have the same set of hypermethylated CpG islands as in a glioma. (wikipedia.org)
  • Our data support a possible role of DNMT3B in nonrandom de novo CpG island methylation leading to colorectal cancer. (umn.edu)
  • CpGcluster uses only integer arithmetic, thus being a fast and computationally efficient algorithm able to predict statistically significant clusters of CpG dinucleotides. (ugr.es)
  • Recent works have suggested the role of epigenetic modification at a CpG island located in POLG gene, encoding the polymerase responsible for mtDNA synthesis. (bmj.com)
  • Most of these elements remain protected from CpG methylation, a prevalent epigenetic modification associated with transcriptional silencing. (fpwr.org)
  • Here we report that the promoter methylation of Plk4 CpG islands increases with age, was more prevalent in males and that Plk4 epigenetic modification and subsequent downregulation of expression was associated with the development of HCC in Plk4 mutant mice. (biomedcentral.com)
  • We have analyzed 375 genes and 58 pseudogenes from the human entries in the EMBL Database for the presence of CpG islands. (nih.gov)
  • The lack of methylation in CpG islands leads to a less compact chromatin structure, and generally allows for active gene expression. (encyclopedia.com)
  • The role of DNA methylation in the control of mammalian gene expression has been the subject of intensive research in recent years, partly due to the critical role of CpG island methylation in the inactivation of tumour suppressor genes during the development of cancer. (biochemsoctrans.org)
  • In fact, about 50 percent of all genes contain a CpG island in their promoter regions. (encyclopedia.com)
  • The great majority of CpG islands colocalise with transcription initiation sites and the origins of DNA replication. (els.net)
  • In normal tissues, the vast majority of CpG islands are completely unmethylated with some exceptions. (wikipedia.org)
  • The locations of G/C boxes, composed of the sequence GGGCGG or its reverse complement CCGCCC, were investigated relative to the location of CpG islands. (nih.gov)
  • This detailed volume examines bioinformatic and molecular biological methods useful to identify and to explore the functions of CpG islands, key navigation points to understand gene regulation in fundamental processes such as development and cell differentiation as well as in diseases like cancer. (springer.com)
  • Possible functions of CpG islands in transcriptional and post-transcriptional regulation of gene expression were discussed, and were related to theories for the maintenance of CpG islands as "methylation-free zones" in germline DNA. (nih.gov)
  • Some factors such as recombination rate and chromosome size might have influenced the evolution of CpG islands in the course of mammalian evolution. (biomedcentral.com)
  • Beginning with a historical perspective and important properties of CpG islands, the book continues with sections on computational and wet lab methods related to the study of DNA methylation, and in-depth protocols for the analysis of CpG island functional features including epigenetic profiling and chromatin interactions. (springer.com)
  • Therefore, none of the main statistical properties of CpG islands (neither G+C content, CpG fraction nor length threshold) are needed as search parameters, which may lead to the high specificity and low overlap with spurious Alu elements observed for CpGcluster predictions. (ugr.es)
  • If the CpG island is far away from the promoter or transcriptional start site, it is hard to say whether its methylation has any impact on transcription. (protocol-online.org)
  • DNA methylation of intragenic CpG islands depends on their transcriptional activity during differentiation and disease. (ox.ac.uk)
  • Analysis of a selection of genes suggests that both human and mouse are losing CpG islands over evolutionary time due to de novo methylation in the germ line followed by CpG loss through mutation. (pnas.org)
  • As a result, residual CpG islands are created in areas where methylation is rare, and CpG sites stick (or where C to T mutation is highly detrimental). (wikipedia.org)
  • Mechanism of Polycomb recruitment to CpG islands revealed by inherited disease-associated mutation. (ox.ac.uk)
  • By exploiting a CpG island (CGI) point mutation causing a Mendelian disease, we show that DNA binding of activating transcription factor (TF) determines histone acetylation and nucleosomal depletion commensurate with Polycomb exclusion from the target promoter. (ox.ac.uk)
  • CpG island hypermethylation is an epigenetic control aberration that is important for gene inactivation in cancer cells. (wikipedia.org)
  • Basic as well as translational research will be needed to understand the mechanisms and roles of CpG island hypermethylation in cancer. (wikipedia.org)
  • The discovery of the methylation-associated inactivation of the Von Hippel-Lindau (VHL) gene revived the idea of the hypermethylation of the CpG island promoter being a mechanism to inactivate genes in cancer. (wikipedia.org)
  • Initially, the presence of alterations in the profile of DNA methylation in cancer was seen as a global hypomethylation of the genome that would lead to massive overexpression of oncogenes with a normally hypermethylated CpG island. (wikipedia.org)
  • CpG islands that are hypermethylated can play three roles in cancer: in diagnosis, prognosis and in monitoring. (wikipedia.org)
  • this methylation at CpG islands that's found in cancer. (coursera.org)
  • Furthermore, CpG island hypermethylation patterns in prostate cancer metastases were very similar to the primary prostate cancers and tended to show greater differences between cases than between anatomical sites of metastasis. (aacrjournals.org)
  • However, using GSTP1 CpG island hypermethylation as the only marker for molecular screening and diagnosis of prostate cancer presents some potential limitations. (aacrjournals.org)
  • First, the theoretical maximum sensitivity for the screening test can only be as high as the frequency of GSTP1 CpG island hypermethylation in the primary cancer tissues. (aacrjournals.org)
  • Heterogeneity in the modification and involvement of chromatin components of the CpG island of the silenced human CDH1 gene in cancer cells. (semanticscholar.org)
  • Caldwell, Charles W. / CpG islands : Their potential as biomarkers for cancer . (elsevier.com)
  • The methylation of unmethylated CpG islands leads to the silencing of genes required for proper cell growth control and is a common mechanism in the development of many types of cancer. (encyclopedia.com)
  • However, one sporadic breast cancer cell line, UACC3199, was ≥ 60% methylated at all 30 CpG sites (18 sites were 100% methylated) and was associated with an eightfold decrease in BRCA1 mRNA compared to normal breast cells. (elsevier.com)
  • Using this information, we developed a classifier for distinguishing cancer and healthy tissues based on their CpG islands statuses of the fragmentation. (ist.ac.at)
  • These findings suggest that most of cancer-specific CpG island hypermethylation occur in the stage of BilIN and that CpG island hypermethylation seems to occur earlier than repetitive DNA element hypomethylation. (elsevier.com)
  • Here, we used the methylation-specific oligonucleotide microarray to map the methylation patterns of a CpG island, located within the promoter and the first exon regions of RASSF1A, in normal breast tissue controls, primary tumors, and breast cancer cell lines. (elsevier.com)
  • Thus, G/C boxes appeared to be a feature of CpG islands in general, rather than a feature of the promoter region of housekeeping genes. (nih.gov)
  • I use CpG Island Explorer to predicate CpG islands,but in one gene I did not get CpG island in the promoter region adjacent to exon1 , I only get one CpG island about 4kb upstream the ATG codon, does the CpG region could be representative for study? (protocol-online.org)
  • The promoter region of around 70% of all genes in the human genome is overlapped by a CpG island (CGI). (springer.com)
  • This initial reduction of p16 expression was associated with limited methylation of the p16 promoter region CpG island. (asm.org)
  • Hypermethylation of CpG islands in the promoter region of death-associated protein kinase (DAP-kinase) coupled with the loss of gamma-interferon-induced apoptosis have been reported in B-cell malignancies suggesting a role in pathogenesis or prognosis. (cdc.gov)
  • In normal lymphocytes, the CpG islands in the promoter region were unmethylated, as were the T-cell lymphoblastic lymphoma and anaplastic LCL. (cdc.gov)
  • Dynamic CpG island methylation changes were derived primarily from methylation in the promoter region. (spandidos-publications.com)
  • Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosine. (pubmedcentralcanada.ca)
  • In the human genome, is DNA methylation mostly restricted to the cytosines of CpG dinucleotides. (biomedcentral.com)
  • [19] CpG islands are usually defined as regions with 1) a length greater than 200bp, 2) a G+C content greater than 50%, 3) a ratio of observed to expected CpG greater than 0.6, although other definitions are sometimes used. (wikipedia.org)
  • Each CpG island was then analysed in terms of length, nucleotide composition, frequency of CpG dinucleotides, and location relative to the transcription unit of the associated gene. (nih.gov)
  • CpG islands were generally found in the same position relative to the transcription unit of equivalent genes in different species, with some notable exceptions. (nih.gov)
  • G/C boxes were located both upstream and downstream from the transcription start site of genes with 5' CpG islands. (nih.gov)
  • CpG islands are typically common near transcription start sites and may be associated with promoter regions. (ucsc.edu)
  • All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue-specific or limited expression are associated with islands. (nih.gov)
  • In this latter group of genes, the position of the islands was not biased toward the 5' end of the transcription unit. (nih.gov)
  • Deaton AM, Bird A (2011) CpG islands and the regulation of transcription. (springer.com)
  • METHODOLOGY/PRINCIPAL FINDINGS: Using the genome-scale in vivo DNA methylation data from human brain, we investigated the flanking sequence features of methylation-resistant CpG islands, and discovered that there are several over-represented putative Transcription Factor Binding Sites (TFBSs) in methylation-resistant CpG islands, and a specific group of zinc finger protein binding sites are over-represented in boundary regions ( approximately 400 bp) flanking such CpG islands. (rti.org)
  • CONCLUSIONS/SIGNIFICANCE: Our results suggest a possible mechanism that certain putative zinc finger protein binding sites over-represented in the boundary regions of the methylation-resistant CpG islands may block the spreading of methylation into these islands, and those TFBSs over-represented within the islands may both reinforce the methylation blocking and promote transcription. (rti.org)
  • These islands contain a large number of cytosine and guanine bases, and they are often found at or near transcription start sites. (elifesciences.org)
  • The lack of methylation at CpG islands has long been assumed to have a passive role in gene expression, leaving the DNA easily accessible and available for transcription factors to bind and initiate transcription. (elifesciences.org)
  • The features for prediction include those that have been previously demonstrated effective (CpG island specific attributes, DNA sequence composition patterns, DNA structure patterns, distribution patterns of conserved transcription factor binding sites and conserved elements, and histone methylation status) as well as those that have not been extensively explored but are likely to contribute additional information from a biological point of view (nucleosome positioning propensities, gene functions, and histone acetylation status). (biomedcentral.com)
  • These "islands" commonly occur in promoter regions of genes (regions where RNA polymerase binds to start transcription), which are located at the 5 ′ ("five prime") end of the genes. (encyclopedia.com)
  • We report that a CpG island close to the UCP1 transcription start site is highly conserved in all 29 vertebrates examined apart from the mouse and xenopus. (frontiersin.org)
  • Methylation of promoter CpG islands present in or near promoter regions may also disrupt the binding of transcription factors ( 11 ). (spandidos-publications.com)
  • While some features are common to all Del elements, CpG island patterns within the LTRs were particular to lineage specific clusters. (sigmaaldrich.com)
  • Normally a C (cytosine) base followed immediately by a G (guanine) base (a CpG) is rare in vertebrate DNA because the Cs in such an arrangement tend to be methylated. (ucsc.edu)
  • A CpG island is a Cytosine and Guanine linked by a phosphate in a repeated sequence. (wikipedia.org)
  • CpG sites are DNA regions where a cytosine nucleotide occurs next to a guanine nucleotide. (pubmedcentralcanada.ca)
  • The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction . (wikipedia.org)
  • The CpG notation is therefore to be interpreted as the cytosine being 5 prime to the guanine base. (wikipedia.org)
  • CpG should not be confused with GpC , the latter meaning that a guanine is followed by a cytosine in the 5' → 3' direction of a single-stranded sequence. (wikipedia.org)
  • Demethylation of this island is correlated with reactivation of XIST in human [ 13 ] and mouse [ 14 ] somatic cells. (biomedcentral.com)
  • In vertebrates, around 60-80% of CpG are methylated in somatic cells [15] and DNA methylation appears as a default state that has to be specifically excluded from defined locations. (wikipedia.org)
  • also find low but appreciable levels of PRC1 at most CpG islands genome-wide, in addition to the high levels of PRC1 at selected islands: this suggests that KDM2B may sample the whole genome to find CpG islands where PRC1 can establish silencing. (elifesciences.org)
  • The newly developed methyl CpG immunoprecipitation (MCIp) technique allows for the unbiased genome-wide profiling of CpG methylation in DNA samples where quantity is limited. (academic2.ru)
  • We evaluated the methylation status in the CpG islands of four deregulated genes ( Casp3 , Cldn1 , Pex11a and Nox4 ) using methylation-sensitive high-resolution melting technology for the samples obtained from different stages of hepatocarcinogenesis. (biologists.org)
  • CpG islands are regions where CpGs are present at significantly higher levels than is typical for the genome as a whole. (ucsc.edu)
  • CpG islands represent 1% of the genome and have a high density of nonmethylated CpGs. (els.net)
  • In particular, it has been shown that specific proteins bind to CpG islands to create chromatin environments that are more favourable for the initiation of gene expression. (elifesciences.org)
  • Moreover, a subset of CpG islands can also bind polycomb-group proteins, including the polycomb repressive complex 1 (PRC1) that silence gene expression. (elifesciences.org)
  • This observation led to the speculation that methylation of CpG sites in the promoter of a gene may inhibit gene expression. (wikipedia.org)
  • CpG islands are short, dispersed regions of unmethylated DNA with a high frequency of CpG dinucleotides relative to the bulk genome. (nih.gov)
  • Additionally, by analyzing SNP frequency in CpG islands, we demonstrated that CpG islands in regions under selective pressure show lower genetic variation. (pubmedcentralcanada.ca)
  • hence CpG dinucleotides steadily deaminate to TpG dinucleotides, which is evidenced by the under-representation of CpG dinucleotides in the human genome (they occur at only 21% of the expected frequency). (wikipedia.org)
  • CpG islands (or CG islands) are regions with a high frequency of CpG sites. (wikipedia.org)