TET enzymes, TDG and the dynamics of DNA demethylation

TET enzymes, TDG and the dynamics of DNA demethylation

2013 October 24; 502(7472): 472–479. doi:10.1038/nature12750 | Rahul M. Kohli and Yi Zhang
DNA methylation plays a crucial role in genome stability, transcription, and development. The discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine (5mC) has advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine (5hmC) is a key intermediate in this process, which can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. This review discusses the recent advances in understanding the mechanisms of DNA demethylation, including the roles of TET enzymes and TDG, and their implications for various biological processes such as pre-implantation development, germ cell reprogramming, and cancer. The dynamic regulation of DNA methylation through oxidation, demethylation, and repair offers new insights into the complex dynamics of gene expression and genome stability.DNA methylation plays a crucial role in genome stability, transcription, and development. The discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine (5mC) has advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine (5hmC) is a key intermediate in this process, which can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. This review discusses the recent advances in understanding the mechanisms of DNA demethylation, including the roles of TET enzymes and TDG, and their implications for various biological processes such as pre-implantation development, germ cell reprogramming, and cancer. The dynamic regulation of DNA methylation through oxidation, demethylation, and repair offers new insights into the complex dynamics of gene expression and genome stability.
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Understanding TET enzymes%2C TDG and the dynamics of DNA demethylation