A DNA Repair Complex Functions as an Oct4/Sox2 Coactivator in Embryonic Stem Cells

被引：136

作者：

Fong, Yick W. ^{[1
]}

Inouye, Carla ^{[1
]}

Yamaguchi, Teppei ^{[1
]}

Cattoglio, Claudia ^{[1
]}

Grubisic, Ivan ^{[2
]}

Tjian, Robert ^{[1
,3
]}

机构：

[1] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, UC Berkeley UCSF Grad Program Bioengn, Berkeley, CA 94720 USA

[3] Univ Calif Berkeley, Li Ka Shing Ctr Biomed & Hlth Sci, Berkeley, CA 94720 USA

来源：

CELL | 2011年 / 147卷 / 01期

基金：

瑞士国家科学基金会;

关键词：

NUCLEOTIDE EXCISION-REPAIR; TRANSCRIPTIONAL REGULATORY CIRCUITRY; PROTEIN-INTERACTION NETWORK; NANOG GENE-EXPRESSION; GROUP-C PROTEIN; SELF-RENEWAL; TARGET GENES; XPC PROTEIN; IN-VITRO; PLURIPOTENCY;

D O I：

10.1016/j.cell.2011.08.038

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 multisubunit 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.

引用

页码：120 / 131

页数：12

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