在從扁形蟲到哺乳動(dòng)物在內(nèi)的很多干細(xì)胞中,,染色質(zhì)大部分沒有異染色質(zhì),所以對轉(zhuǎn)錄調(diào)控因子來說它們是完全開放的,。
現(xiàn)在,,對小鼠胚胎細(xì)胞中的新穎調(diào)控因子所做的一項(xiàng)RNA干涉篩選工作表明,,染色質(zhì)重構(gòu)因子Chd1是維持染色質(zhì)開放性和胚胎細(xì)胞多能性所必需的,也是體細(xì)胞重新編程為多能細(xì)胞所必需的,。這是關(guān)于染色質(zhì)開放性及多能性之間存在一個(gè)因果關(guān)系的直接證據(jù),。Chd1在生殖細(xì)胞和成年干細(xì)胞中都高度表達(dá),因而我們看到這樣一個(gè)可能性:染色質(zhì)開放性與干細(xì)胞分化潛力之間的關(guān)系是一個(gè)普遍現(xiàn)象,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.