Chd1调节胚胎干细胞的开放染色质和多能性。
Chd1 regulates open chromatin and pluripotency of embryonic stem cells.
作者信息
Gaspar-Maia Alexandre, Alajem Adi, Polesso Fanny, Sridharan Rupa, Mason Mike J, Heidersbach Amy, Ramalho-Santos João, McManus Michael T, Plath Kathrin, Meshorer Eran, Ramalho-Santos Miguel
机构信息
Department 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.
出版信息
Nature. 2009 Aug 13;460(7257):863-8. doi: 10.1038/nature08212. Epub 2009 Jul 8.
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.
一个基本不含异染色质的开放染色质是干细胞的一个标志。目前尚不清楚开放染色质对于干细胞的分化潜能是否必要，以及维持开放染色质需要哪些分子。在这里，我们表明染色质重塑因子Chd1是维持多能小鼠胚胎干细胞开放染色质所必需的。Chd1是一种常染色质蛋白，与活性基因的启动子相关联，Chd1的下调会导致异染色质的积累。Chd1缺陷的胚胎干细胞不再具有多能性，因为它们无法产生原始内胚层，并且具有很高的神经分化倾向。此外，Chd1是成纤维细胞高效重编程为多能干细胞状态所必需的。我们的结果表明，Chd1对于胚胎干细胞的开放染色质和多能性以及体细胞重编程为多能状态至关重要。
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