May 31, 2017

TET-mediated active DNA demethylation: mechanism, function and beyond

Nature Reviews. Genetics
Xiaoji Wu, Yi Zhang

Abstract

In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine (C) through TET dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution or thymine DNA glycosylase (TDG)-dependent base excision repair. In the past few years, biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation. Additionally, many regulatory mechanisms of this process have been identified. Technological advances in mapping and tracing the oxidized forms of 5mC allow further dissection of their functions. Furthermore, the biological functions of active DNA demethylation in various biological contexts have also been revealed. In this Review, we summarize the recent advances and highlight key unanswered questions.

  • References266
  • Citations233

Mentioned in this Paper

Study
DNA Methylation [PE]
N, N-bis(2-aminoethyl)-1,3-propanediamine
Metabolic Networks and Pathways
Base Excision Repair
Virus Replication
Cytosine
DNA Methylation
5-carboxylcytosine
Oxidation

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