TET enzymes, TDG and the dynamics of DNA demethylation

被引：1325

作者：

Kohli, Rahul M. ^{[1
,2
]}

Zhang, Yi ^{[3
,4
,5
,6
,7
]}

机构：

[1] Univ Penn, Dept Med, Raymond & Ruth Perelman Sch Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Dept Biochem & Biophys, Raymond & Ruth Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Howard Hughes Med Inst, Boston, MA 02115 USA

[4] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA

[5] Boston Childrens Hosp, Div Hematol Oncol, Dept Pediat, Boston, MA 02115 USA

[6] Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA

[7] Harvard Stem Cell Inst, Boston, MA 02115 USA

来源：

NATURE | 2013年 / 502卷 / 7472期

关键词：

HEMATOPOIETIC STEM-CELLS; THYMINE DNA; ACTIVE-DEMETHYLATION; CXXC DOMAIN; 5-METHYLCYTOSINE OXIDATION; PATERNAL GENOME; SELF-RENEWAL; METHYLATION; MOUSE; 5-HYDROXYMETHYLCYTOSINE;

D O I：

10.1038/nature12750

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that 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. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.

引用

页码：472 / 479

页数：8

共 104 条

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