title: A DNA repair complex functions as an Oct4/Sox2 coactivator in embryonic stem cells.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Yick W
authors.initials: YW
authors.lastname: Fong
authors.forename: Carla
authors.initials: C
authors.lastname: Inouye
authors.forename: Teppei
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Claudia
authors.initials: C
authors.lastname: Cattoglio
authors.forename: Ivan
authors.initials: I
authors.lastname: Grubisic
authors.forename: Robert
authors.initials: R
authors.lastname: Tjian
mesh_terms: D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming; D004260:DNA Repair; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D042822:Genomic Instability; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors