Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development

被引：210

作者：

Xu, Yufei ^{[2
]}

Xu, Chao ^{[1
,3
]}

Kato, Akiko ^{[4
]}

Tempel, Wolfram ^{[1
,3
]}

Abreu, Jose Garcia ^{[5
]}

Bian, Chuanbing ^{[1
,3
]}

Hu, Yeguang ^{[2
]}

Hu, Di ^{[2
,6
]}

Zhao, Bin ^{[6
]}

Cerovina, Tanja ^{[1
,3
]}

Diao, Jianbo ^{[6
]}

Wu, Feizhen ^{[6
]}

He, Housheng Hansen ^{[7
,8
]}

Cui, Qingyan ^{[9
]}

Clark, Erin ^{[2
]}

Ma, Chun ^{[2
,6
]}

Barbara, Andrew ^{[2
]}

Veenstra, Gert Jan C. ^{[10
]}

Xu, Guoliang ^{[9
]}

Kaiser, Ursula B. ^{[2
]}

Liu, X. Shirley ^{[7
,8
,11
]}

Sugrue, Stephen P. ^{[12
]}

He, Xi ^{[5
]}

Min, Jinrong ^{[1
,3
]}

Kato, Yoichi ^{[4
]}

Shi, Yujiang Geno ^{[2
]}

机构：

[1] Univ Toronto, Struct Genom Consortium, Toronto, ON M5G 1L7, Canada

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

[3] Univ Toronto, Dept Physiol, Toronto, ON M5G 1L7, Canada

[4] Florida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32306 USA

[5] Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA

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

[7] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[8] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA

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

[10] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands

[11] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA

[12] Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA

来源：

CELL | 2012年 / 151卷 / 06期

基金：

英国惠康基金;

关键词：

EMBRYONIC STEM-CELLS; DNA METHYLATION; MAMMALIAN DNA; SELF-RENEWAL; 5-HYDROXYMETHYLCYTOSINE; MOUSE; 5-METHYLCYTOSINE; PROTEINS; GENOME; 5-CARBOXYLCYTOSINE;

D O I：

10.1016/j.cell.2012.11.014

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：

Ten-Eleven Translocation (Tet) family of dioxygenases dynamically regulates DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functions and mechanisms of action in gene regulation and embryonic development are largely unknown. Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes. Tet3 is an active 5mC hydroxylase regulating the 5mC/5hmC status at target gene promoters. Biochemical and structural studies further demonstrate that the Tet3 CXXC domain is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are both crucial for Tet3's biological function. Together, these findings define Tet3 as a transcription regulator and reveal a molecular mechanism by which the 5mC hydroxylase and DNA binding activities of Tet3 cooperate to control target gene expression and embryonic development.

引用

页码：1200 / 1213

页数：14

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