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Molecular and Cellular Biology, January 2007, p. 651-661, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01257-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Functional Differentiation of SWI/SNF Remodelers in Transcription and Cell Cycle Control{triangledown} ,{dagger}

Yuri M. Moshkin,1,{ddagger} Lisette Mohrmann,1,{ddagger} Wilfred F. J. van Ijcken,2 and C. Peter Verrijzer1*

Department of Biochemistry, Center for Biomedical Genetics,1 Center for Biomics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands2

Received 11 July 2006/ Returned for modification 4 August 2006/ Accepted 26 October 2006

Drosophila BAP and PBAP represent two evolutionarily conserved subclasses of SWI/SNF chromatin remodelers. The two complexes share the same core subunits, including the BRM ATPase, but differ in a few signature subunits: OSA defines BAP, whereas Polybromo (PB) and BAP170 specify PBAP. Here, we present a comprehensive structure-function analysis of BAP and PBAP. An RNA interference knockdown survey revealed that the core subunits BRM and MOR are critical for the structural integrity of both complexes. Whole-genome expression profiling suggested that the SWI/SNF core complex is largely dysfunctional in cells. Regulation of the majority of target genes required the signature subunit OSA, PB, or BAP170, suggesting that SWI/SNF remodelers function mostly as holoenzymes. BAP and PBAP execute similar, independent, or antagonistic functions in transcription control and appear to direct mostly distinct biological processes. BAP, but not PBAP, is required for cell cycle progression through mitosis. Because in yeast the PBAP-homologous complex, RSC, controls cell cycle progression, our finding reveals a functional switch during evolution. BAP mediates G2/M transition through direct regulation of string/cdc25. Its signature subunit, OSA, is required for directing BAP to the string/cdc25 promoter. Our results suggest that the core subunits play architectural and enzymatic roles but that the signature subunits determine most of the functional specificity of SWI/SNF holoenzymes in general gene control.

* Corresponding author. Mailing address: Department of Biochemistry, Center for Biomedical Genetics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31-10-4087461. Fax: 31-10-4089472. E-mail: c.verrijzer{at}erasmusmc.nl.

{triangledown} Published ahead of print on 13 November 2006.

{dagger} Supplemental material for this article can be found at http://mcb.asm.org.

{ddagger} Y.M.M. and L.M. contributed equally to this work.

Molecular and Cellular Biology, January 2007, p. 651-661, Vol. 27, No. 2
0270-7306/07/$08.00+0     doi:10.1128/MCB.01257-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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