The RSC Complex Localizes to Coding Sequences to Regulate Pol II and Histone Occupancy

ATP-dependent chromatin remodelers regulate chromatin structure during multiple stages of transcription. We report that RSC, an essential chromatin remodeler, is recruited to the open reading frames (ORFs) of actively transcribed genes genome wide, suggesting a role for RSC in regulating transcription elongation. Consistent with such a role, Pol II occupancy in the ORFs of weakly transcribed genes is drastically reduced upon depletion of the RSC catalytic subunit Sth1. RSC inactivation also reduced histone H3 occupancy across transcribed regions. Remarkably, the strongest effects on Pol II and H3 occupancy were confined to the genes displaying the greatest RSC ORF enrichment. Additionally, RSC recruitment to the ORF requires the activities of the SAGA and NuA4 HAT complexes and is aided by the activities of the Pol II CTD Ser2 kinases Bur1 and Ctk1. Overall, our findings strongly implicate ORF-associated RSC in governing Pol II function and in maintaining chromatin structure over transcribed regions. [Display omitted] •RSC is recruited to the coding sequences of actively transcribed genes•HATs and serine 2 kinases promote RSC recruitment to coding regions•ORF-bound RSC regulates RNA polymerase II and histone occupancy RSC is the only essential chromatin remodeling complex in yeast. Spain et al. show that RSC is recruited to the coding regions of transcribed genes by HATs and Pol II CTD kinases. RSC associated with coding regions facilitates Pol II transcription and also preserves histone density in the transcribed sequences.