The expanding scope and impact of epigenetic cytosine modifications.
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.
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.
Monica Yun
MY
Liu
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.
Jamie E
JE
DeNizio
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.
Emily K
EK
Schutsky
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.
Rahul M
RM
Kohli
D000818:Animals; D003596:Cytosine / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans
D003596:Cytosine