Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells
Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells
复制标题
DOI：
10.1073/pnas.1505569112
复制
发表时间：
2015-05-05
影响因子：
11.1
通讯作者：
Tjian, Robert
中科院分区：
文献类型：
--
作者：
Cattoglio, Claudia;Zhang, Elisa T.;Tjian, Robert
胚胎干细胞（ESC）状态由OCT 4、SOX 2和NANOG与辅因子、染色质调节因子、非编码RNA和信号传导途径的其他效应物转录控制。揭示这些调控回路的组成部分及其相互作用为部署ESC和诱导多能干细胞提供了知识基础。我们最近确定了DNA修复复合物着色性干皮病C（XPC）-RAD 23 B-CETN 2作为OCT 4/SOX 2转录激活所需的干细胞共激活因子（SCC）。在这里，我们调查SCC基因组范围内的作用，在小鼠胚胎干细胞的映射区域结合的RAD 23 B和分析SCC-耗尽的胚胎干细胞的转录谱。我们建立OCT 4和SOX 2作为主要的转录因子招募SCC的多能性基因的调控区域，并确定XPC亚基与这两种蛋白质的相互作用是必不可少的。本研究揭示了SCC转录活性的新机制和功能方面，从而强调了这种调控复合物的多样化功能。
The embryonic stem cell (ESC) state is transcriptionally controlled by OCT4, SOX2, and NANOG with cofactors, chromatin regulators, noncoding RNAs, and other effectors of signaling pathways. Uncovering components of these regulatory circuits and their interplay provides the knowledge base to deploy ESCs and induced pluripotent stem cells. We recently identified the DNA-repair complex xeroderma pigmentosum C (XPC)-RAD23B-CETN2 as a stem cell coactivator (SCC) required for OCT4/SOX2 transcriptional activation. Here we investigate the role of SCC genome-wide in murine ESCs by mapping regions bound by RAD23B and analyzing transcriptional profiles of SCC-depleted ESCs. We establish OCT4 and SOX2 as the primary transcription factors recruiting SCC to regulatory regions of pluripotency genes and identify the XPC subunit as essential for interaction with the two proteins. The present study reveals new mechanistic and functional aspects of SCC transcriptional activity, and thus underscores the diversified functions of this regulatory complex.