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...

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Veröffentlicht in:Stem cells (Dayton, Ohio) Jg. 26; H. 5; S. 1155 - 1165
Hauptverfasser: Yan, Zhijiang, Wang, Zhong, Sharova, Lioudmila, Sharov, Alexei A., Ling, Chen, Piao, Yulan, Aiba, Kazuhiro, Matoba, Ryo, Wang, Weidong, Ko, Minoru S. H.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Bristol John Wiley & Sons, Ltd 01.05.2008
Schlagworte:
Animals
ARID1B
BAF250B
Biomarkers - metabolism
Cell Cycle
Cell Differentiation
Cell Proliferation
Chromatin Assembly and Disassembly
Chromatin remodeling
Chromosomal Proteins, Non-Histone - metabolism
DNA microarray
DNA-Binding Proteins - metabolism
Down-Regulation
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Gene Expression Profiling
Gene targeting
HeLa Cells
Humans
Mice
Pluripotent Stem Cells - cytology
SWI/SNF
Transcription Factors - genetics
Transcription Factors - metabolism
Up-Regulation
ISSN:1066-5099, 1549-4918, 1549-4918
Online-Zugang:Volltext
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Zusammenfassung: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. Disclosure of potential conflicts of interest is found at the end of this article.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
equal contributions.
ISSN:1066-5099
1549-4918
1549-4918
DOI:10.1634/stemcells.2007-0846