title: Functional and mechanistic studies of XPC DNA-repair complex as transcriptional coactivator in embryonic stem cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cattoglio
authors.affiliation: 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.
authors.forename: Elisa T
authors.initials: ET
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ivan
authors.initials: I
authors.lastname: Grubisic
authors.affiliation: 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.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Chiba
authors.affiliation: Brigham Regenerative Medicine Center, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, MA 02139.
authors.forename: Yick W
authors.initials: YW
authors.lastname: Fong
authors.affiliation: 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, jmlim@berkeley.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Tjian
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D019070:Cell Lineage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D016086:Lentivirus / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D039904:Pluripotent Stem Cells / Q000166:cytology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; C499250:Rad23b protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors; C086984:XPC protein, human
keywords: ChIP-seq; RNA-seq; pluripotency; protein–protein interactions; transcription