Transcriptional repression by the BRG1-SWI/SNF complex affects the pluripotency of human embryonic stem cells

Xiaoli Zhang; Bing Li; Wenguo Li; Lijuan Ma; Dongyan Zheng; Leping Li; Weijing Yang; Min Chu; Wei Chen; Richard B Mailman; Jun Zhu; Guoping Fan; Trevor K Archer; Yuan Wang

doi:10.1016/j.stemcr.2014.07.004

Transcriptional repression by the BRG1-SWI/SNF complex affects the pluripotency of human embryonic stem cells

Stem Cell Reports. 2014 Sep 9;3(3):460-74. doi: 10.1016/j.stemcr.2014.07.004. Epub 2014 Aug 14.

Authors

Xiaoli Zhang¹, Bing Li¹, Wenguo Li¹, Lijuan Ma¹, Dongyan Zheng¹, Leping Li², Weijing Yang³, Min Chu¹, Wei Chen¹, Richard B Mailman⁴, Jun Zhu³, Guoping Fan⁵, Trevor K Archer⁶, Yuan Wang⁷

Affiliations

¹ Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
² Biostatistics Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
³ Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
⁴ Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033-0850, USA.
⁵ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-7088, USA.
⁶ 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.
⁷ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Cell Line
Cell Proliferation
DNA Helicases / analysis
DNA Helicases / genetics*
DNA Helicases / metabolism
DNA-Binding Proteins
Embryonic Stem Cells / cytology*
Embryonic Stem Cells / metabolism
Humans
Mice
Mice, SCID
Nuclear Proteins / analysis
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
RNA Interference*
RNA, Small Interfering / genetics
Transcription Factors / analysis
Transcription Factors / genetics*
Transcription Factors / metabolism
Transcriptional Activation

Substances

DNA-Binding Proteins
Nuclear Proteins
RNA, Small Interfering
SMARCC1 protein, human
SMARCC2 protein, human
Transcription Factors
SMARCA4 protein, human
DNA Helicases

Abstract

Publication types

MeSH terms

Substances

Grants and funding