Cattoglio Claudia, Zhang Elisa T, Grubisic Ivan, Chiba Kunitoshi, Fong Yick W, Tjian Robert
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, Li Ka Shing Center for Biomedical and Health Sciences, California Institute of Regenerative Medicine Center of Excellence.
Department of Molecular and Cell Biology, Howard Hughes Medical Institute, Li Ka Shing Center for Biomedical and Health Sciences, California Institute of Regenerative Medicine Center of Excellence, University of California Berkeley-University of California, San Francisco Graduate Program in Bioengineering, University of California, Berkeley, CA 94720; and.
Proc Natl Acad Sci U S A. 2015 May 5;112(18):E2317-26. doi: 10.1073/pnas.1505569112. Epub 2015 Apr 21.
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.
胚胎干细胞（ESC）状态受OCT4、SOX2和NANOG以及辅助因子、染色质调节剂、非编码RNA和信号通路的其他效应器的转录调控。揭示这些调控回路的组成部分及其相互作用，为利用胚胎干细胞和诱导多能干细胞提供了知识库。我们最近鉴定出DNA修复复合物着色性干皮病C（XPC）-RAD23B-CETN2是OCT4/SOX2转录激活所需的干细胞共激活因子（SCC）。在这里，我们通过绘制RAD23B结合区域并分析SCC缺失的胚胎干细胞的转录谱，研究了SCC在小鼠胚胎干细胞全基因组中的作用。我们确定OCT4和SOX2是将SCC招募到多能性基因调控区域的主要转录因子，并确定XPC亚基对于与这两种蛋白质的相互作用至关重要。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。
