Histone Acetyltransferases Gcn5 and Esa1 Regulate Occupancy of RSC to Maintain Nucleosome-Depleted Regions and Promote RSC Recruitment to Coding Regions Genome-Wide in

Chromatin remodelers are important for maintaining chromatin structure and regulating gene expression. In this study, we investigated the roles of histone acetyltransferases (HATs) Gcn5 and Esa1 in regulating RSC and histone occupancy on chromatin, as well as their impact on transcription across the genome. Our findings reveal distinct effects of HATs on RSC occupancy in promoters and ORFs. The lack of HATs leads to the accumulation of RSC, and it was greater in nucleosome-depleted regions (NDRs) containing fragile nucleosomes (FNs), relative to other NDRs. The increased RSC NDR-binding was greater in Esa1-deficient cells than in those lacking Gcn5. The increased RSC binding was not seen in cells lacking the H3 or H4 tails. The mutants also led to significant increases in histone occupancies around the NDRs genome-wide. Overall, the data suggest that hypoacetylated tails may recruit RSC to NDRs, especially to FN-containing NDRs, and that subsequent histone acetylation enhances histone eviction. The HAT mutants also exhibited reduced recruitment of TBP and Pol II. In contrast to the promoters, RSC occupancies were significantly reduced in transcribed ORFs in the HAT mutants. Thus, our data implicate HATs and RSC in maintaining NDRs, regulating chromatin structure, and promoting transcription.