BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain undifferentiated mouse embryonic stem cells.
Whether SWI/SNF chromatin remodeling complexes play roles in embryonic stem (ES) cells remains unknown. Here we show that SWI/SNF complexes are present in mouse ES cells, and their composition is dynamically regulated upon induction of ES cell differentiation. For example, the SWI/SNF purified from undifferentiated ES cells contains a high level of BAF155 and a low level of BAF170 (both of which are homologs of yeast SWI3 protein), whereas that from differentiated cells contains nearly equal amounts of both. Moreover, the levels of BAF250A and BAF250B decrease during the differentiation of ES cells, whereas that of BRM increases. The altered expression of SWI/SNF components hinted that these complexes could play roles in ES cell maintenance or differentiation. We therefore generated ES cells with biallelic inactivation of BAF250B and found that these cells display a reduced proliferation rate and an abnormal cell cycle. Importantly, these cells are deficient in the self-renewal capacity of undifferentiated ES cells and exhibit certain phenotypes of differentiated cells, including reduced expression of several pluripotency-related genes and increased expression of some differentiation-related genes. These data suggest that the BAF250B-associated SWI/SNF is essential for mouse ES cells to maintain their normal proliferation and pluripotency. The work presented here underscores the importance of SWI/SNF chromatin remodeling complexes in pluripotent stem cells.
Yan
Zhijiang
Z
Genome Instability and Chromatin-Remodeling Section, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Wang
Zhong
Z
Sharova
Lioudmila
L
Sharov
Alexei A
AA
Ling
Chen
C
Piao
Yulan
Y
Aiba
Kazuhiro
K
Matoba
Ryo
R
Wang
Weidong
W
Ko
Minoru S H
MS
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D015415:Biomarkers; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; C491090:Smarcc1 protein, mouse; C587872:Smarcc2 protein, mouse; D014157:Transcription Factors