Chromatin remodelers are essential for the maintenance of chromatin structure and gene regulation. In this study, we examined the role of histone acetyltransferases (HATs) Gcn5 and Esa1 in regulating RSC and histone occupancies and their effects on transcription genome-wide. We identified contrasting roles of HATs in modulating RSC occupancies in promoters and ORFs. In HAT mutants, RSC accumulated in nucleosome depleted regions (NDRs) with fragile nucleosomes (FNs) more than those with stable -1 nucleosomes. Moreover, the accumulation was more significant in the Esa1 mutant than in the Gcn5 mutant. However, RSC NDR accumulation was not observed in cells lacking H3 or H4 tails. Furthermore, we observed marked increases in histone occupancies in NDRs in the HAT mutants genome-wide. Overall, these data suggest that FNs use hypoacetylated tails to recruit RSC to NDRs, and subsequent acetylation of the tails promote histone eviction. In contrast to the promoters, RSC occupancies were significantly reduced in transcribed ORFs in the HAT mutants. Additionally, the HAT mutants showed reduced TBP and Pol II binding at promoters. Thus, our data implicate HATs and RSC in maintaining NDRs, regulating chromatin structure, and promoting transcription.