title: Transcriptional repression by the BRG1-SWI/SNF complex affects the pluripotency of human embryonic stem cells.
abstract: The SWI/SNF complex plays an important role in mouse embryonic stem cells (mESCs), but it remains to be determined whether this complex is required for the pluripotency of human ESCs (hESCs). Using RNAi, we demonstrated that depletion of BRG1, the catalytic subunit of the SWI/SNF complex, led to impaired self-renewing ability and dysregulated lineage specification of hESCs. A unique composition of the BRG1-SWI/SNF complex in hESCs was further defined by the presence of BRG1, BAF250A, BAF170, BAF155, BAF53A, and BAF47. Genome-wide expression analyses revealed that BRG1 participated in a broad range of biological processes in hESCs through pathways different from those in mESCs. In addition, chromatin immunoprecipitation sequencing (ChIP-seq) demonstrated that BRG1 played a repressive role in transcriptional regulation by modulating the acetylation levels of H3K27 at the enhancers of lineage-specific genes. Our data thus provide valuable insights into molecular mechanisms by which transcriptional repression affects the self-renewal and differentiation of hESCs.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Wenguo
authors.initials: W
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Ma
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Leping
authors.initials: L
authors.lastname: Li
authors.affiliation: Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: Weijing
authors.initials: W
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033-0850, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Mailman
authors.affiliation: Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-7088, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Fan
authors.affiliation: Chromatin and Gene Expression Group, Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
authors.forename: Trevor K
authors.initials: TK
authors.lastname: Archer
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: ywang@bio.ecnu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D004265:DNA Helicases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C101681:SMARCC1 protein, human; C101682:SMARCC2 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases