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

Abstract

Heterochromatin 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 fibers in 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 the SIR genes (SIR2, SIR3, and SIR4) 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 of SIR genes partially rescues the growth defects of swi2, ino80, and hst3/hst4 mutants during replication stress conditions. Interestingly, partial suppression of swi2, ino80, and hst3 hst4 mutant phenotypes is due to the pseudo-diploid state of sir mutants, 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.