Mammalian cytosine methylation at a glance

Ooi, Steen K.T.; O’Donnell, Anne H.; Bestor, Timothy H.

doi:10.1242/jcs.015123

Cited by 216 publications

(170 citation statements)

References 58 publications

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“…In contrast, 5mC shows a conserved association with condensed and transcriptionally silent chromatin across eukaryotes 42, 94, 123. However, while apparently contrary in their functional consequences, 5mC and m 6 A do not seem to be correlated in eukaryotes.…”

Section: What Are the Roles For M6a In Eukaryotic Dna?mentioning

confidence: 84%

“…Of these, 5mC was found to be widely distributed across eukaryotes, including humans and other mammals, thereby making it the subject of intense investigation 39, 40. While 5mC in eukaryotes was found to be generated by enzymes having evolutionary links to prokaryotic R‐M and counter R‐M MTases 41, it was found to be an important epigenetic mark with diverse functional consequences in different eukaryotes 42, 43, 44, 45. Recent work has shown that 5mC is not a terminal modification: it is further oxidized by action of the TET/JBP family of 2‐oxoglutarate and Fe (II)‐dependent dioxygenases (2OGFeDOs) to give rise to 5hmC, 5‐formylcytosine (5fC), and 5‐carboxylcytosine (5caC) 46, 47, 48, 49, 50.…”

Section: Introductionmentioning

confidence: 99%

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Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

2015

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While N6‐methyladenosine (m6A) is a well‐known epigenetic modification in bacterial DNA, it remained largely unstudied in eukaryotes. Recent studies have brought to fore its potential epigenetic role across diverse eukaryotes with biological consequences, which are distinct and possibly even opposite to the well‐studied 5‐methylcytosine mark. Adenine methyltransferases appear to have been independently acquired by eukaryotes on at least 13 occasions from prokaryotic restriction‐modification and counter‐restriction systems. On at least four to five instances, these methyltransferases were recruited as RNA methylases. Thus, m6A marks in eukaryotic DNA and RNA might be more widespread and diversified than previously believed. Several m6A‐binding protein domains from prokaryotes were also acquired by eukaryotes, facilitating prediction of potential readers for these marks. Further, multiple lineages of the AlkB family of dioxygenases have been recruited as m6A demethylases. Although members of the TET/JBP family of dioxygenases have also been suggested to be m6A demethylases, this proposal needs more careful evaluation.Also watch the Video Abstract.

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Section: What Are the Roles For M6a In Eukaryotic Dna?mentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

2015

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“…Molecular mechanisms may include direct interactions between DNMT and diverse regulatory factors, as well as the involvement of histone-modifying enzymes, and proteins involved in the biogenesis of small RNA (42). In addition, DNMT have been shown to interact with transcription factors, the innate specificity of which for defined DNA sequences could participate in the preferential targeting of DNA methylation to specific gene promoters (15).…”

Section: Discussionmentioning

confidence: 99%

Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues

Velasco

Hubé

Rollin

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

122

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Methylation of cytosine residues within the CpG dinucleotide in mammalian cells is an important mediator of gene expression, genome stability, X-chromosome inactivation, genomic imprinting, chromatin structure, and embryonic development. The majority of CpG sites in mammalian cells is methylated in a nonrandom fashion, raising the question of how DNA methylation is distributed along the genome. Here, we focused on the functions of DNA methyltransferase-3b (Dnmt3b), of which deregulated activity is linked to several human pathologies. We generated Dnmt3b hypomorphic mutant mice with reduced catalytic activity, which first revealed a deregulation of Hox genes expression, consistent with the observed homeotic transformations of the posterior axis. In addition, analysis of deregulated expression programs in Dnmt3b mutant embryos, using DNA microarrays, highlighted illegitimate activation of several germ-line genes in somatic tissues that appeared to be linked directly to their hypomethylation in mutant embryos. We provide evidence that these genes are direct targets of Dnmt3b. Moreover, the recruitment of Dnmt3b to their proximal promoter is dependant on the binding of the E2F6 transcriptional repressor, which emerges as a common hallmark in the promoters of genes found to be up-regulated as a consequence of impaired Dnmt3b activity. Therefore, our results unraveled a coordinated regulation of genes involved in meiosis, through E2F6-dependant methylation and transcriptional silencing in somatic tissues.DNA methylation | immunodeficiency | centromeric instability | facial anomalies | E2F family | hypomorphic mutation | hox genes

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“…Until recently, the only known modified base in DNA was 5-methylcytosine (5mC), an epigenetic mark established by DNA methyltransferases (DNMTs) (3). 5mC represents 5-8% of total cytosine in different cell types and in somatic cells is almost exclusively found in the CpG sequence context (4)(5)(6).…”

mentioning

confidence: 99%

Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation

Tsagaratou

Äijö

Lio

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

142

165

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The discovery of Ten Eleven Translocation proteins, enzymes that oxidize 5-methylcytosine (5mC) in DNA, has revealed novel mechanisms for the regulation of DNA methylation. We have mapped 5-hydroxymethylcytosine (5hmC) at different stages of T-cell development in the thymus and T-cell differentiation in the periphery. We show that 5hmC is enriched in the gene body of highly expressed genes at all developmental stages and that its presence correlates positively with gene expression. Further emphasizing the connection with gene expression, we find that 5hmC is enriched in active thymus-specific enhancers and that genes encoding key transcriptional regulators display high intragenic 5hmC levels in precursor cells at those developmental stages where they exert a positive effect. Our data constitute a valuable resource that will facilitate detailed analysis of the role of 5hmC in T-cell development and differentiation.thymic development | epigenetics

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Mammalian cytosine methylation at a glance

Cited by 216 publications

References 58 publications

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

Adenine methylation in eukaryotes: Apprehending the complex evolutionary history and functional potential of an epigenetic modification

Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues

Dissecting the dynamic changes of 5-hydroxymethylcytosine in T-cell development and differentiation

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