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Curr Opin Chem Biol. 2016 Aug;33:67-73. doi: 10.1016/j.cbpa.2016.05.029. Epub 2016 Jun 14.

The expanding scope and impact of epigenetic cytosine modifications.

Author information

1
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
2
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: rkohli@upenn.edu.

Abstract

Chemical modifications to genomic DNA can expand and shape its coding potential. Cytosine methylation in particular has well-established roles in regulating gene expression and defining cellular identity. The discovery of TET family enzymes opened a major frontier beyond DNA methylation, revealing three oxidized forms of cytosine that could mediate DNA demethylation or encode independent epigenetic functions. Chemical biology has been instrumental in uncovering TET's intricate reaction mechanisms and scope of reactivity on a surprising variety of substrates. Moreover, innovative chemoenzymatic strategies have enabled sensitive detection of oxidized cytosine products in vitro and in vivo. We highlight key recent developments that demonstrate how chemical biology is advancing our understanding of the extended, dynamic epigenome.

PMID:
27315338
PMCID:
PMC5018417
DOI:
10.1016/j.cbpa.2016.05.029
[Indexed for MEDLINE]
Free PMC Article

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