在从扁形虫到哺乳动物在内的很多干细胞中,染色质大部分没有异染色质,所以对转录调控因子来说它们是完全开放的。
现在,对小鼠胚胎细胞中的新颖调控因子所做的一项RNA干涉筛选工作表明,染色质重构因子Chd1是维持染色质开放性和胚胎细胞多能性所必需的,也是体细胞重新编程为多能细胞所必需的。这是关于染色质开放性及多能性之间存在一个因果关系的直接证据。Chd1在生殖细胞和成年干细胞中都高度表达,因而我们看到这样一个可能性:染色质开放性与干细胞分化潜力之间的关系是一个普遍现象。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 460, 863-868 (13 August 2009) | doi:10.1038/nature08212
Chd1 regulates open chromatin and pluripotency of embryonic stem cells
Alexandre Gaspar-Maia1,2,3, Adi Alajem4, Fanny Polesso1,2, Rupa Sridharan5, Mike J. Mason5, Amy Heidersbach2, Jo?o Ramalho-Santos6, Michael T. McManus2, Kathrin Plath5, Eran Meshorer4 & Miguel Ramalho-Santos1,2
1 Departments of Ob/Gyn and Pathology, Center for Reproductive Sciences and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143-0525, USA
2 Diabetes Center, University of California, San Francisco, California 94143-0534, USA
3 PhD Programme in Biomedicine and Experimental Biology (BEB), Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
4 Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
5 Department of Biological Chemistry and Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, PO Box 951737, Los Angeles, California 90095, USA
6 Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
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.