Molecular Biology

Demethylation DNA Dynamics

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Science  27 May 2011:
Vol. 332, Issue 6033, pp. 1013
DOI: 10.1126/science.332.6033.1013-a

The methylation of DNA on cytosine (C) bases, most often at CpG sites, plays an important role in the epigenetic regulation of genomic imprinting, suppression of transposons and other parasitic DNA sequences, and X chromosome inactivation. Addition and removal of DNA methylation can be highly dynamic, but the means by which the methyl mark is removed in animals is unclear. One possible route involves the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (Tet) enzyme family.

Xu et al. map the binding of Tet1 across the genome of mouse embryonic stem cells and, along with Pastor et al., map the genome-wide occurrence of 5hmC. Tet1 bound to unmodified CpG, to 5mCpG, and to 5hmCpG. Tet1 was enriched at promoters and in gene bodies, and its binding correlated with high CpG levels. Besides being enriched in gene bodies (and particularly exons), 5hmC was found at transcription start sites and at silenced promoters and at poised (but inactive) promoters in particular. Its occurrence at some enhancers further reinforces the idea that the presence of 5hmC might prime some quiescent loci for rapid activation.

Mol. Cell 42, 1 (2011); Nature 10.1038/nature10102 (2011).

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