A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells.
A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells.
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DOI：
10.1016/j.cell.2011.08.038
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发表时间：
2011-09-30
期刊：
影响因子：
64.5
通讯作者：
Tjian R
中科院分区：
文献类型：
--
作者：
Fong YW;Inouye C;Yamaguchi T;Cattoglio C;Grubisic I;Tjian R
转录激活因子Oct 4、Sox 2和Nanog与多种辅因子合作，协调胚胎干细胞（ES）特异性基因表达程序，形成多能性的分子基础。在这里，我们报告使用一个公正的体外转录生化互补试验，发现一个多亚基干细胞辅激活因子复合物（SCC），选择性地需要的Nanog基因的协同激活Oct 4和Sox 2。SCC的纯化、鉴定和重建揭示了该共激活因子是三聚体的XC-核苷酸切除修复复合物。SCC与Oct 4和Sox 2直接相互作用，并被募集到Nanog和Oct 4启动子以及被Oct 4和Sox 2占据的大部分基因组区域。SCC/XPC的耗尽损害ES细胞中的多能性和成纤维细胞向诱导多能干（iPS）细胞的体细胞重编程。本研究鉴定了一种转录辅激活因子，其在维持ES细胞多能性和保护基因组完整性方面具有多种功能。
The transcriptional activators Oct4, Sox2 and Nanog cooperate with a wide array of cofactors to orchestrate an embryonic stem (ES) cell-specific gene expression program that forms the molecular basis of pluripotency. Here we report using an unbiased in vitro transcription-biochemical complementation assay to discover a multi-subunit stem cell coactivator complex (SCC) that is selectively required for the synergistic activation of the Nanog gene by Oct4 and Sox2. Purification, identification and reconstitution of SCC revealed this coactivator to be the trimeric XPC-nucleotide excision repair complex. SCC interacts directly with Oct4 and Sox2 and is recruited to the Nanog and Oct4 promoters as well as a majority of genomic regions that are occupied by Oct4 and Sox2. Depletion of SCC/XPC compromised both pluripotency in ES cells and somatic cell reprogramming of fibroblasts to induced pluripotent stem (iPS) cells. This study identifies a transcriptional coactivator with diversified functions in maintaining ES cell pluripotency and safeguarding genome integrity.
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DOI：
10.1038/nrg2847
发表时间：
2010-08
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Araki, M;Masutani, C;Hanaoka, F
通讯作者：
Hanaoka, F
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
21.3
作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui
影响因子：
11.4
作者：
Camenisch, Ulrike;Traeutlein, Daniel;Naegeli, Hanspeter
通讯作者：
Naegeli, Hanspeter