Chd1 regulates open chromatin and pluripotency of embryonic stem cells

被引：380

作者：

Gaspar-Maia, Alexandre ^{[1
,2
,3
,4
,5
]}

Alajem, Adi ^{[6
]}

Polesso, Fanny ^{[1
,2
,3
,4
]}

Sridharan, Rupa ^{[7
,8
]}

Mason, Mike J. ^{[7
,8
]}

Heidersbach, Amy ^{[4
]}

Ramalho-Santos, Joao

McManus, Michael T. ^{[4
]}

Plath, Kathrin ^{[7
,8
]}

Meshorer, Eran ^{[6
]}

Ramalho-Santos, Miguel ^{[1
,2
,3
,4
]}

机构：

[1] Univ Calif San Francisco, Dept Ob Gyn, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Pathol, Ctr Reprod Sci, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

[4] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA

[5] Univ Coimbra, PhD Programme Biomed & Expt Biol, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal

[6] Hebrew Univ Jerusalem, Dept Genet, Inst Life Sci, IL-91904 Jerusalem, Israel

[7] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA

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

来源：

NATURE | 2009年 / 460卷 / 7257期

基金：

以色列科学基金会;

关键词：

SELF-RENEWAL; EXPRESSION; TRANSCRIPTION; DIFFERENTIATION; FIBROBLASTS; GENERATION; LYSINE-4; PROTEIN;

D O I：

10.1038/nature08212

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：

An open chromatin largely devoid of heterochromatin is a hallmark of stem cells. It remains unknown whether an open chromatin is necessary for the differentiation potential of stem cells, and which molecules are needed to maintain open chromatin. Here we show that the chromatin remodelling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells. Chd1 is a euchromatin protein that associates with the promoters of active genes, and downregulation of Chd1 leads to accumulation of heterochromatin. Chd1-deficient embryonic stem cells are no longer pluripotent, because they are incapable of giving rise to primitive endoderm and have a high propensity for neural differentiation. Furthermore, Chd1 is required for efficient reprogramming of fibroblasts to the pluripotent stem cell state. Our results indicate that Chd1 is essential for open chromatin and pluripotency of embryonic stem cells, and for somatic cell reprogramming to the pluripotent state.

引用

页码：863 / U97

页数：8

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