Genome-wide Regulation of 5hmC, 5mC, and Gene Expression by Tet1 Hydroxylase in Mouse Embryonic Stem Cells

被引：481

作者：

Xu, Yufei ^{[2
]}

Wu, Feizhen ^{[1
]}

Tan, Li ^{[1
]}

Kong, Lingchun ^{[1
]}

Xiong, Lijun ^{[1
]}

Deng, Jie ^{[5
]}

Barbera, Andrew J. ^{[2
]}

Zheng, Lijuan ^{[1
]}

Zhang, Haikuo ^{[2
]}

Huang, Stephen ^{[4
]}

Min, Jinrong ^{[6
]}

Nicholson, Thomas ^{[7
]}

Chen, Taiping ^{[7
]}

Xu, Guoliang ^{[8
]}

Shi, Yang ^{[1
,3
]}

Zhang, Kun ^{[5
]}

Shi, Yujiang Geno ^{[1
,2
]}

机构：

[1] Fudan Univ, Lab Epigenet, Inst Biomed Sci, Shanghai 200032, Peoples R China

[2] Harvard Univ, Sch Med, Div Endocrinol Diabet & Hypertens, Brigham & Womens Hosp, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Div Newborn Med, Childrens Hosp Boston, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Div Thyroid, Childrens Hosp Boston, Boston, MA 02115 USA

[5] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92903 USA

[6] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada

[7] Novartis Inst Biomed Res, Epigenet Program, Cambridge, MA 02139 USA

[8] Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

来源：

MOLECULAR CELL | 2011年 / 42卷 / 04期

基金：

美国国家卫生研究院;

关键词：

DNA METHYLATION; RNA-SEQ; SELF-RENEWAL; 5-HYDROXYMETHYLCYTOSINE; 5-METHYLCYTOSINE; BINDING; DIFFERENTIATION; QUANTIFICATION; SPECIFICATION; TRANSCRIPTION;

D O I：

10.1016/j.molcel.2011.04.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA methylation at the 5 position of cytosine (5mC) in the mammalian genome is a key epigenetic event critical for various cellular processes. The ten-eleven translocation (Tet) family of 5mC-hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), offers a way for dynamic regulation of DNA methylation. Here we report that Tet1 binds to unmodified C or 5mC- or 5hmC-modified CpG-rich DNA through its CXXC domain. Genome-wide mapping of Tet1 and 5hmC reveals mechanisms by which Tet1 controls 5hmC and 5mC levels in mouse embryonic stem cells (mESCs). We also uncover a comprehensive gene network influenced by Tet1. Collectively, our data suggest that Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting 5mC to 5hmC through hydroxylase activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 targets, ultimately contributing to mESC differentiation and the onset of embryonic development.

引用

页码：451 / 464

页数：14

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