Wang Li, Du Ying, Ward James M, Shimbo Takashi, Lackford Brad, Zheng Xiaofeng, Miao Yi-liang, Zhou Bingying, Han Leng, Fargo David C, Jothi Raja, Williams Carmen J, Wade Paul A, Hu Guang
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Integrative Bioinformatics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Cell Stem Cell. 2014 May 1;14(5):575-91. doi: 10.1016/j.stem.2014.02.013.
The master transcription factors play integral roles in the pluripotency transcription circuitry of embryonic stem cells (ESCs). How they selectively activate expression of the pluripotency network while simultaneously repressing genes involved in differentiation is not fully understood. Here, we define a requirement for the INO80 complex, a SWI/SNF family chromatin remodeler, in ESC self-renewal, somatic cell reprogramming, and blastocyst development. We show that Ino80, the chromatin remodeling ATPase, co-occupies pluripotency gene promoters with the master transcription factors, and its occupancy is dependent on OCT4 and WDR5. At the pluripotency genes, Ino80 maintains an open chromatin architecture and licenses recruitment of Mediator and RNA polymerase II for gene activation. Our data reveal an essential role for INO80 in the expression of the pluripotency network and illustrate the coordination among chromatin remodeler, transcription factor, and histone-modifying enzyme in the regulation of the pluripotent state.
主转录因子在胚胎干细胞（ESC）的多能性转录调控网络中发挥着不可或缺的作用。它们如何在选择性激活多能性网络基因表达的同时抑制参与分化的基因，目前尚不完全清楚。在此，我们确定了INO80复合物（一种SWI/SNF家族染色质重塑因子）在ESC自我更新、体细胞重编程和囊胚发育中的必要性。我们发现，染色质重塑ATP酶Ino80与主转录因子共同占据多能性基因启动子，其占据情况依赖于OCT4和WDR5。在多能性基因处，Ino80维持开放的染色质结构，并允许中介体和RNA聚合酶II募集以激活基因。我们的数据揭示了INO80在多能性网络基因表达中的关键作用，并阐明了染色质重塑因子、转录因子和组蛋白修饰酶在多能状态调控中的协同作用。
