Removal of a methyl group from one or more nucleotides within a DNA molecule.
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DNA methylation is the addition of a methyl group to the DNA that happens at cytosine. The image shows a cytosine single ring base and a methyl group added on to the 5 carbon. In mammals, DNA methylation occurs almost exclusively at a cytosine that is followed by a guanine.
For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequence or, in replicating cells, by preventing addition of methyl groups to DNA so that the replicated DNA will largely have cytosine in the DNA sequence (5mC will be diluted out).
Methylated cytosine is frequently present in the linear DNA sequence where a cytosine is followed by a guanine in a 5' → 3' direction (a CpG site). In mammals, DNA methyltransferases (which add methyl groups to DNA bases) exhibit a strong sequence preference for cytosines at CpG sites.[1] There appear to be more than 20 million CpG dinucleotides in the human genome (see genomic distribution). In mammals, on average, 70% to 80% of CpG cytosines are methylated,[2] though the level of methylation varies with different tissues. Methylated cytosines often occur in groups or CpG islands within the promoter regions of genes, where such methylation may reduce or silence gene expression (see gene expression). Methylated cytosines in the gene body, however, are positively correlated with expression.[3]
Almost 100% DNA demethylation occurs by a combination of passive dilution and active enzymatic removal during the reprogramming that occurs in early embryogenesis and in gametogenesis. Another large demethylation, of about 3% of all genes, can occur by active demethylation in neurons during formation of a strong memory.[4] After surgery, demethylations are found in peripheral blood mononuclear cells at sites annotated to immune system genes.[5] Demethylations also occur during the formation of cancers.[6] During global DNA hypomethylation of tumor genomes, there is a minor to moderate reduction of the number of methylated cytosines (5mC) amounting to a loss of about 5% to 20% on average of the 5mC bases.[7]
^Ziller MJ, Müller F, Liao J, Zhang Y, Gu H, Bock C, Boyle P, Epstein CB, Bernstein BE, Lengauer T, Gnirke A, Meissner A (December 2011). "Genomic distribution and inter-sample variation of non-CpG methylation across human cell types". PLOS Genet. 7 (12): e1002389. doi:10.1371/journal.pgen.1002389. PMC 3234221. PMID 22174693.
^Jabbari K, Bernardi G (May 2004). "Cytosine methylation and CpG, TpG (CpA) and TpA frequencies". Gene. 333: 143–9. doi:10.1016/j.gene.2004.02.043. PMID 15177689.
^Yang X, Han H, De Carvalho DD, Lay FD, Jones PA, Liang G (October 2014). "Gene body methylation can alter gene expression and is a therapeutic target in cancer". Cancer Cell. 26 (4): 577–90. doi:10.1016/j.ccr.2014.07.028. PMC 4224113. PMID 25263941.
^Duke CG, Kennedy AJ, Gavin CF, Day JJ, Sweatt JD (July 2017). "Experience-dependent epigenomic reorganization in the hippocampus". Learn. Mem. 24 (7): 278–288. doi:10.1101/lm.045112.117. PMC 5473107. PMID 28620075.
^Sadahiro R, Knight B, James F, Hannon E, Charity J, Daniels IR, Burrage J, Knox O, Crawford B, Smart NJ, Mill J (April 2020). "Major surgery induces acute changes in measured DNA methylation associated with immune response pathways". Sci Rep. 10 (1): 5743. Bibcode:2020NatSR..10.5743S. doi:10.1038/s41598-020-62262-x. PMC 7113299. PMID 32238836.
^Ehrlich M (December 2009). "DNA hypomethylation in cancer cells". Epigenomics. 1 (2): 239–59. doi:10.2217/epi.09.33. PMC 2873040. PMID 20495664.
^Pfeifer GP (April 2018). "Defining Driver DNA Methylation Changes in Human Cancer". Int J Mol Sci. 19 (4): 1166. doi:10.3390/ijms19041166. PMC 5979276. PMID 29649096.
mammals, DNAdemethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNAdemethylation can...
hydrogen atoms. The counterpart of demethylation is methylation. Demethylation is relevant to epigenetics. Demethylation of DNA is catalyzed by demethylases...
dioxygenases. They are instrumental in DNAdemethylation. 5-Methylcytosine (see first Figure) is a methylated form of the DNA base cytosine (C) that often regulates...
fertilizes an ovum to form a zygote, rapid DNAdemethylation of the paternal DNA and slower demethylation of the maternal DNA occurs until formation of a morula...
the rat brain. Some specific mechanisms guiding new DNA methylations and new DNAdemethylations in the hippocampus during memory establishment have been...
synaptic plasticity; is modified by experiences; and active DNA methylation and demethylation is required for memory formation and maintenance. In 2016...
agent Differentially methylated regions DNAdemethylationDNA methylation reprogramming Epigenetics, of which DNA methylation is a significant contributor...
in epigenetic DNAdemethylation, which is relevant to learning and memory In mammalian nuclear DNA, a methyl group can be added, by a DNA methyltransferase...
proteins also participate(s) in epigenetic alterations involving DNA methylation, demethylation or reactions coupled to histone modification. Nishida et al...
remain a matter of current research while it seems to be involved in DNAdemethylation and therefore gene regulation. TET1 was first discovered in a 61-year-old...
increased about 3.5-fold in DNA and this caused about 80% demethylation of the 5-methylcytosines in the genome. Demethylation of CpGs in a gene promoter...
genome-wide reprogramming. Reprogramming involves global DNAdemethylation facilitated by the DNA base excision repair pathway as well as chromatin reorganization...
mouse, demethylation of DNA, particularly at sites of methylated cytosines, is likely a key process in establishing totipotency. Demethylation involves...
"Demethylation of 5-Methylcytosine (5mC) in neuron DNA," especially the TET dependent pathway, have been confirmed as pathways of DNAdemethylation. A...
increased about 3.5-fold in DNA and this caused about 80% demethylation of the 5-methylcytosines in the genome. Demethylation of CpGs in a gene promoter...
involves genome-wide DNAdemethylation, chromatin reorganization and epigenetic imprint erasure leading to totipotency. DNAdemethylation is carried out by...
through demethylation of its CpG island promoter at exon IV and demethylation depends on base excision repair (see figure). The activity of the DNA glycosylase...
genome-wide DNAdemethylation, followed by subsequent new methylation to reset the epigenome in order to form an egg or sperm. In the mouse, PGCs undergo DNA demethylation...
Recombinant FTO protein was first discovered to catalyze demethylation of 3-methylthymine in single-stranded DNA, and 3-methyluridine in single-stranded RNA, with...
totipotency. Reprogramming is facilitated by active DNAdemethylation, a process that entails the DNA base excision repair pathway. This pathway is employed...
epigenetic imprints. Reprogramming is facilitated by active DNAdemethylation involving the DNA base excision repair enzymatic pathway. This pathway entails...
PMID 35098021. Bayraktar G, Kreutz MR (2018). "The Role of Activity-Dependent DNADemethylation in the Adult Brain and in Neurological Disorders". Front Mol Neurosci...
DNA glycosylase enzymes have been implicated in the repression of gene silencing in A. thaliana, N. tabacum and other plants by active demethylation....
uniparental disomy at 4q24. TET2 may also be a candidate for active DNAdemethylation, the catalytic removal of the methyl group added to the fifth carbon...
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