| A role for BAF57 in cell cycle-dependent transcriptional regulation by the SWI/SNF chromatin remodeling complex. | |
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MedLine Citation:
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PMID: 20460533 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The SWI/SNF complex is an ATP-dependent chromatin remodeling complex that plays pivotal roles in gene regulation and cell cycle control. In the present study, we explored the molecular functions of the BAF57 subunit of SWI/SNF in cell cycle control via transcriptional regulation of cell cycle-related genes. We affinity purified SWI/SNF from HeLa cells stably expressing FLAG-tagged BAF47/Ini1 with or without stable short hairpin RNA-mediated knockdown of BAF57. The subunit composition of the holo-SWI/SNF and BAF57-depleted SWI/SNF complexes from these cells was determined using a quantitative SILAC (stable isotope labeling by amino acids in cell culture)-based proteomic approach. Depletion of BAF57 resulted in a significant codepletion of BAF180 from the SWI/SNF complex without decreasing total cellular BAF180 levels. In biochemical assays of SWI/SNF activity, the holo-SWI/SNF and BAF57/BAF180-depleted SWI/SNF complexes exhibited similar activities. However, in cell proliferation assays using HeLa cells, knockdown of BAF57 resulted in an accumulation of cells in the G(2)-M phase, inhibition of colony formation, and impaired growth in soft agar. Knockdown of BAF57 also caused transcriptional misregulation of various cell cycle-related genes, especially genes involved in late G(2). Collectively, our results have identified a new role for BAF57 within the SWI/SNF complex that is required for (a) maintaining the proper subunit composition of the complex and (b) cell cycle progression through the transcriptional regulation of a subset of cell cycle-related genes. |
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Authors:
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Nasun Hah; Annemieke Kolkman; Donald D Ruhl; W W M Pim Pijnappel; Albert J R Heck; H Th Marc Timmers; W Lee Kraus |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-11 |
Journal Detail:
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Title: Cancer research Volume: 70 ISSN: 1538-7445 ISO Abbreviation: Cancer Res. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-02 Completed Date: 2010-06-17 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 4402-11 Citation Subset: IM |
Copyright Information:
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Copyright 2010 AACR. |
Affiliation:
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Department of Molecular Biology and Genetics and Graduate Field of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Cycle
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genetics* Chromatin Immunoprecipitation Chromosomal Proteins, Non-Histone / genetics* DNA-Binding Proteins / genetics* Gene Expression Regulation, Neoplastic Hela Cells Humans Nuclear Proteins / genetics Transcription Factors / genetics* Transcription, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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DK058110/DK/NIDDK NIH HHS; R01 DK058110-06/DK/NIDDK NIH HHS; R01 DK058110-07/DK/NIDDK NIH HHS; R01 DK058110-08/DK/NIDDK NIH HHS; R01 DK058110-09/DK/NIDDK NIH HHS; R01 DK058110-10/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chromosomal Proteins, Non-Histone; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/PBRM1 protein, human; 0/SMARCE1 protein, human; 0/SWI-SNF-B chromatin-remodeling complex; 0/Transcription Factors |
| Comments/Corrections | |
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