A Role for BAF57 in Cell Cycle–Dependent Transcriptional Regulation by the SWI/SNF Chromatin Remodeling Complex
| Autor: | Donald D. Ruhl, H. Th. Marc Timmers, Albert J. R. Heck, W.W.M. Pim Pijnappel, Annemieke Kolkman, Nasun Hah, W. Lee Kraus |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Chromatin Immunoprecipitation
Cancer Research Transcription Genetic Chromosomal Proteins Non-Histone cells genetic processes macromolecular substances Article Chromatin remodeling Humans Chromatin structure remodeling (RSC) complex Scaffold/matrix attachment region ChIA-PET biology Chemistry Cell Cycle fungi Nuclear Proteins food and beverages Mi-2/NuRD complex SWI/SNF Chromatin Cell biology DNA-Binding Proteins Gene Expression Regulation Neoplastic enzymes and coenzymes (carbohydrates) Oncology biology.protein biological phenomena cell phenomena and immunity HeLa Cells Transcription Factors Bivalent chromatin |
| Zdroj: | Cancer Research. 70:4402-4411 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-09-2767 |
| Popis: | 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 G2-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 G2. 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. Cancer Res; 70(11); 4402–11. ©2010 AACR. |
| Databáze: | OpenAIRE |
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