Distinct roles of the methylcytosine oxidases Tet1 and Tet2 in mouse embryonic stem cells

被引：200

作者：

Huang, Yun ^{[1
,3
]}

Chavez, Lukas ^{[1
,3
]}

Chang, Xing ^{[1
,3
]}

Wang, Xue ^{[1
]}

Pastor, William A. ^{[1
,4
,5
,6
]}

Kang, Jinsuk ^{[1
]}

Zepeda-Martinez, Jorge A. ^{[1
]}

Pape, Utz J. ^{[7
,8
]}

Jacobsen, Steven E. ^{[4
,5
,6
]}

Peters, Bjoern ^{[2
]}

Rao, Anjana ^{[1
,3
]}

机构：

[1] La Jolla Inst Allergy & Immunol, Div Signalling & Gene Express, La Jolla, CA 92037 USA

[2] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA

[3] Sanford Consortium Regenerat Med, La Jolla, CA 92037 USA

[4] Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA

[6] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA 90095 USA

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

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

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 04期

基金：

美国国家卫生研究院;

关键词：

DNA methylation; DNA hydroxymethylation; epigenetics; DNA demethylation; MYELOID CANCERS; POSTNATAL-DEVELOPMENT; DNA DEMETHYLATION; BASE-RESOLUTION; MAMMALIAN DNA; 5-HYDROXYMETHYLCYTOSINE; GENOME; 5-METHYLCYTOSINE; METHYLATION; CHROMATIN;

D O I：

10.1073/pnas.1322921111

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：

07 ; 0710 ; 09 ;

摘要：

Dioxygenases of the Ten-Eleven Translocation (TET) family are 5-methylcytosine oxidases that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidation products in DNA. We show that Tet1 and Tet2 have distinct roles in regulating 5hmC in mouse embryonic stem cells (mESC). Tet1 depletion diminishes 5hmC levels at transcription start sites (TSS), whereas Tet2 depletion is predominantly associated with decreased 5hmC in gene bodies. Enrichment of 5hmC is observed at the boundaries of exons that are highly expressed, and Tet2 depletion results in substantial loss of 5hmC at these boundaries. In contrast, at promoter/TSS regions, Tet2 depletion results in increased 5hmC, potentially because of the redundant activity of Tet1. Together, the data point to a complex interplay between Tet1 and Tet2 in mESC, and to distinct roles for these two proteins in regulating promoter, exon, and polyadenylation site usage in cells.

引用

页码：1361 / 1366

页数：6

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