Functional differentiation of SWI/SNF remodelers in transcription and cell cycle control.
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 G(2)/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.
Moshkin
Yuri M
YM
Department of Biochemistry, Center for Biomedical Genetics, Erasmus University Medical Center, 3000 DR Rotterdam, The Netherlands.
Mohrmann
Lisette
L
van Ijcken
Wilfred F J
WF
Verrijzer
C Peter
CP
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D020035:Holoenzymes / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D011401:Promoter Regions, Genetic; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C485119:BAP170 protein, Drosophila; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D020035:Holoenzymes; D021122:Protein Subunits; D015534:Trans-Activators; C086469:brm protein, Drosophila; C462943:mor protein, Drosophila; C117995:osa protein, Drosophila; D000251:Adenosine Triphosphatases