SWI/SNF antagonizes SIR heterochromatin to promote transcription of genes expressed during mitotic exit inSaccharomyces cerevisiae

Abstract

ABSTRACTHeterochromatin is a repressive, specialized chromatin structure that is central to eukaryotic transcriptional regulation and genome stability. In the budding yeast,Saccharomyces cerevisiae, heterochromatin formation requires Sir2p, Sir3p, and Sir4p, and these Sir proteins create specialized chromatin structures at telomeres and silent mating type loci. Previously, we reported that the SWI/SNF chromatin remodeling enzyme can evict Sir3 from chromatin fibersin vitro, though whether this activity contributes to the role of SWI/SNF as a transcriptional activator at euchromatic loci is unknown. Here, we characterize genetic interactions between theSIRgenes (SIR2,SIR3, andSIR4) and genes encoding subunits of the chromatin remodelers SWI/SNF and INO80C, as well genes encoding the histone deacetylases Hst3 and Hst4. We find that loss ofSIRgenes partially rescues the growth defects ofswi2,ino80, andhst3/hst4mutants during replication stress conditions. Interestingly, partial suppression ofswi2,ino80, andhst3 hst4mutant phenotypes is due to the pseudo-diploid state ofsirmutants, but a significant portion is due to more direct functional interactions. Consistent with this view, transcriptional profiling of strains lacking Swi2 or Sir3 identifies a set of genes whose expression in the M/G1 phase of the cell cycle requires SWI/SNF to antagonize the repressive impact of Sir3.