Global role for chromatin remodeling enzymes in mitotic gene expression

Regulation of eukaryotic gene expression requires ATP-dependent chromatin remodeling enzymes, such as SWI/SNF, and histone acetyltransferases, such as Gcn5p. Here we show that SWI/SNF remodeling controls recruitment of Gcn5p HAT activity to many genes in late mitosis and that these chromatin remodeling enzymes play a role in regulating mitotic exit. In contrast, interphase expression of GAL1, HIS3, PHO5, and PHO8 is accompanied by SWI/SNF-independent recruitment of Gcn5p HAT activity. Surprisingly, prearresting cells in late mitosis imposes a requirement for SWI/SNF in recruiting Gcn5p HAT activity to the GAL1 promoter, and GAL1 expression also becomes dependent on both chromatin remodeling enzymes. We propose that SWI/SNF and Gcn5p are globally required for mitotic gene expression due to the condensed state of mitotic chromatin.     

Acetylation of Rsc4p by Gcn5p is essential in the absence of histone H3 acetylation

Rsc4p, a subunit of the RSC chromatin-remodeling complex, is acetylated at lysine 25 by Gcn5p, a well-characterized histone acetyltransferase (HAT). Mutation of lysine 25 does not result in a significant growth defect, and therefore whether this modification is important for the function of the essential RSC complex was unknown. In a search to uncover the molecular basis for the lethality resulting from loss of multiple histone H3-specific HATs, we determined that loss of Rsc4p acetylation is lethal in strains lacking histone H3 acetylation. Phenotype comparison of mutants with arginine and glutamine substitutions of acetylatable lysines within the histone H3 tail suggests that it is a failure to neutralize the charge of the H3 tail that is lethal in strains lacking Rsc4p acetylation. We also demonstrate that Rsc4p acetylation does not require any of the known Gcn5p-dependent HAT complexes and thus represents a truly novel function for Gcn5p. These results demonstrate for the first time the vital and yet redundant functions of histone H3 and Rsc4p acetylation in maintaining cell viability.