A two-step regulatory mechanism dynamically controls histone H3 acetylation by SAGA complex at growth-related promoters

Acetylation of histone H3 at residue K9 (H3K9ac) is a dynamically regulated mark associated with transcriptionally active promoters in eukaryotes. However, our understanding of the relation-ship between H3K9ac and gene expression remains largely correlative. In this study, we identify a large suite of growth-related genes in yeast that undergo a particularly strong down-regulation of both transcription and H3K9ac upon stress, and delineate the roles of transcriptional activa-tors, repressors, SAGA histone acetyltransferase, and RNA-polymerase II in this response. We demonstrate that H3K9 acetylation states are orchestrated by a two-step mechanism driven by the dynamic binding of transcriptional repressors and activators, that is independent of tran-scription. In response to stress, promoter release of transcriptional activators at growth-related genes is a prerequisite for rapid reduction of H3K9ac, whereas binding of transcriptional re-pressors is required to establish a hypo-acetylated, strongly repressed state.