Exceptional epigenetics in the brain

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Science  05 Jun 2015:
Vol. 348, Issue 6239, pp. 1094-1095
DOI: 10.1126/science.aac5832

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Cytosine (C) methylation, or mC, is a modification of DNA that regulates gene expression in various contexts such as development, cancer, and imprinting. In most mammalian somatic tissues, mC arises only when C is in a dinucleotide context followed by the nucleotide guanine (G), and the vast majority of these sites are methylated (mCG). However, in the adult mammalian brain, noncanonical cytosine methylation in a non-CG context occurs at a high level [mCH; H = adenine (A), C, or thymine (T)]. The quantity of non-CG methylation is inversely correlated with gene expression, but the mechanism by which mCH controls transcription has not been clear. Two recent studies (1, 2) suggest a mechanistic link between mCH and gene expression and substantially revise our view of gene regulation by DNA methylation in the brain, which was previously formed only on the basis of studies of mCG.