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Review
. 2014 Oct 1;6(10):a018630.
doi: 10.1101/cshperspect.a018630.

Expanding the epigenetic landscape: novel modifications of cytosine in genomic DNA

Skirmantas Kriaucionis  1 , Mamta Tahiliani  2
Affiliations
Review

Expanding the epigenetic landscape: novel modifications of cytosine in genomic DNA

Skirmantas Kriaucionis et al. Cold Spring Harb Perspect Biol. .

Abstract

Methylation of the base cytosine in DNA is critical for silencing endogenous retroviruses, regulating gene expression, and establishing cellular identity, and has long been regarded as an indelible epigenetic mark. The recent discovery that the ten eleven translocation (TET) proteins can oxidize 5-methylcytosine (5mC) resulting in the formation of 5-hydroxymethylcytosine (5hmC) and other oxidized cytosine variants in the genome has triggered a paradigm shift in our understanding of how dynamic changes in DNA methylation regulate transcription and cellular differentiation, thus influencing normal development and disease.

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Figures

Figure 1.
Figure 1.
Distribution and metabolism of cytosine modifications within genes in ES cells and neurons. (A) TET-mediated oxidation of 5mC followed by base excision repair (BER)-mediated removal of 5caC keeps promoters and enhancers free of methylation in ES cells. It is also possible that oxidation of 5mC blocks maintenance methylation at these regions. MeCP2 binds both 5mC (B) and 5hmC (C) in neuronal gene bodies, where the cytosine modification state correlates with the level of expression.
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