Nutrient starvation-induced Hda1C rewiring: coordinated regulation of transcription and translation

In yeast, Hda1 histone deacetylase complex (Hda1C) plays an important role in transcriptional regulation by modulating histone acetylation. We here explored the changes in Hda1C binding in nutrient-rich and -starved conditions. Chromatin immunoprecipitation sequencing revealed that starvation alters RNA Pol II and Hda1C binding to coding genes in a highly correlated manner. Interestingly, we discovered RNA Pol II transcription-independent recruitment of Hda1C to intergenic regions, particularly the upstream regulatory sequences (URS) of ribosomal protein (RP) genes, which are enriched with Rap1 binding sites. Under nutrient starvation, Rap1 contributes to the recruitment of Hda1C to these URS regions, where Hda1C deacetylates histones, thereby fine-tuning basal gene expression and delaying RP gene reactivation. Furthermore, Hda1C is also required for RNA Pol I transcription of ribosomal RNAs (rRNAs) and RNA Pol III transcription of transfer RNA (tRNA) genes, especially in nutrient-limited conditions. Significantly, Hda1C mutants are sensitive to translation inhibitors and display altered ribosome profiles. Thus, Hda1C may coordinate transcriptional regulation within the nucleus with translation control in the cytoplasm and could be a key regulator of gene expression responses to nutrient stress.