Wdr5 Mediates Self-Renewal and Reprogramming via the Embryonic Stem Cell Core Transcriptional Network

被引：466

作者：

Ang, Yen-Sin ^{[1
,2
,3
]}

Tsai, Su-Yi ^{[1
,3
,5
]}

Lee, Dung-Fang ^{[1
,2
,3
]}

Monk, Jonathan ^{[1
,2
]}

Su, Jie ^{[1
,2
,3
]}

Ratnakumar, Kajan ^{[1
,4
,5
]}

Ding, Junjun ^{[1
,3
]}

Ge, Yongchao ^{[6
]}

Darr, Henia ^{[1
,2
,3
]}

Chang, Betty ^{[1
,2
,3
]}

Wang, Jianlong ^{[1
,3
]}

Rendl, Michael ^{[1
,3
,5
]}

Bernstein, Emily ^{[1
,4
,5
]}

Schaniel, Christoph ^{[1
,2
]}

Lemischka, Ihor R. ^{[1
,2
,3
]}

机构：

[1] Mt Sinai Sch Med, Black Family Stem Cell Inst, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA

[3] Mt Sinai Sch Med, Dept Dev & Regenerat Biol, New York, NY 10029 USA

[4] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA

[5] Mt Sinai Sch Med, Dept Dermatol, New York, NY 10029 USA

[6] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA

来源：

CELL | 2011年 / 145卷 / 02期

关键词：

CHROMATIN-STRUCTURE; DEVELOPMENTAL REGULATORS; HISTONE H3; POLYCOMB; GENES; PLURIPOTENT; BINDING; GENOME; RECOGNITION; METHYLATION;

D O I：

10.1016/j.cell.2011.03.003

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：

The embryonic stem (ES) cell transcriptional and chromatin-modifying networks are critical for self-renewal maintenance. However, it remains unclear whether these networks functionally interact and, if so, what factors mediate such interactions. Here, we show that WD repeat domain 5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively correlates with the undifferentiated state and is a regulator of ES cell self-renewal. We demonstrate that Wdr5, an "effector" of H3K4 methylation, interacts with the pluripotency transcription factor Oct4. Genome-wide protein localization and transcriptome analyses demonstrate overlapping gene regulatory functions between Oct4 and Wdr5. The Oct4-Sox2-Nanog circuitry and trxG cooperate in activating transcription of key self-renewal regulators, and furthermore, Wdr5 expression is required for the efficient formation of induced pluripotent stem (iPS) cells. We propose an integrated model of transcriptional and epigenetic control, mediated by select trxG members, for the maintenance of ES cell self-renewal and somatic cell reprogramming.

引用

页码：183 / 197

页数：15

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