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Nat Rev Genet. 2017 Sep;18(9):517-534. doi: 10.1038/nrg.2017.33. Epub 2017 May 30.

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

Wu X1,2,3,4,5, Zhang Y1,2,3,4.

Author information

1
Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.
2
Program in Cellular and Molecular Medicine, Boston Children's Hospital, WAB-149G, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
3
Harvard Stem Cell Institute, Boston, Massachusetts 02115, USA.
4
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
5
Ph.D. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts 02115, USA.

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.

PMID:
28555658
DOI:
10.1038/nrg.2017.33
[Indexed for MEDLINE]

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