A role for BAF57 in cell cycle-dependent transcriptional regulation by the SWI/SNF chromatin remodeling complex

Nasun Hah, Annemieke Kolkman, Donald D. Ruhl, W. W M Pim Pijnappel, Albert J R Heck, H. Th Marc Timmers, W. Lee Kraus

Research output: Contribution to journalArticle

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Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)4402-4411
Number of pages10
JournalCancer Research
Volume70
Issue number11
DOIs
StatePublished - Jun 1 2010

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cdc Genes
Chromatin Assembly and Disassembly
Cell Cycle
Cell Cycle Checkpoints
HeLa Cells
Isotope Labeling
G2 Phase
Cell Division
Proteomics
Small Interfering RNA
Genes
Agar
Cell Culture Techniques
Adenosine Triphosphate
Cell Proliferation
Amino Acids
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A role for BAF57 in cell cycle-dependent transcriptional regulation by the SWI/SNF chromatin remodeling complex. / Hah, Nasun; Kolkman, Annemieke; Ruhl, Donald D.; Pijnappel, W. W M Pim; Heck, Albert J R; Timmers, H. Th Marc; Kraus, W. Lee.

In: Cancer Research, Vol. 70, No. 11, 01.06.2010, p. 4402-4411.

Research output: Contribution to journalArticle

Hah, Nasun ; Kolkman, Annemieke ; Ruhl, Donald D. ; Pijnappel, W. W M Pim ; Heck, Albert J R ; Timmers, H. Th Marc ; Kraus, W. Lee. / A role for BAF57 in cell cycle-dependent transcriptional regulation by the SWI/SNF chromatin remodeling complex. In: Cancer Research. 2010 ; Vol. 70, No. 11. pp. 4402-4411.
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