A Role for BAF57 in Cell Cycle-Dependent Transcriptional Regulation by the SWI/SNF Chromatin Remodeling Complex

被引：35

作者：

Hah, Nasun ^{[1
,2
]}

Kolkman, Annemieke ^{[3
,4
,7
]}

Ruhl, Donald D. ^{[1
]}

Pijnappel, W. W. M. Pim ^{[6
,7
]}

Heck, Albert J. R. ^{[3
,4
,5
,7
]}

Timmers, H. Th Marc ^{[6
,7
]}

Kraus, W. Lee ^{[1
,2
,8
]}

机构：

[1] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA

[2] Cornell Univ, Grad Field Biochem Mol & Cell Biol, Ithaca, NY 14853 USA

[3] Univ Utrecht, Biomol Mass Spectrometry & Prote Grp, Bijvoet Ctr Biomol Res, Utrecht, Netherlands

[4] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands

[5] Ctr Biomed Genet, Utrecht, Netherlands

[6] Univ Med Ctr Utrecht, Dept Physiol Chem, Utrecht, Netherlands

[7] Netherlands Prote Ctr, Utrecht, Netherlands

[8] Cornell Univ, Dept Pharmacol, Weill Med Coll, New York, NY 10021 USA

来源：

CANCER RESEARCH | 2010年 / 70卷 / 11期

基金：

美国国家科学基金会;

关键词：

TUMOR-SUPPRESSOR GENE; BREAST-CANCER; YEAST RSC; SUBUNIT; PROTEIN; EXPRESSION; BINDING; SPECIFICITY; BAF180; FAMILY;

D O I：

10.1158/0008-5472.CAN-09-2767

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Cancer Res; 70(11); 4402-11. (C) 2010 AACR.

引用

页码：4402 / 4411

页数：10

共 43 条

[1] Targeting of SWI/SNF chromatin remodelling complexes to estrogen-responsive genes [J].