Reference: Zencir S, et al. (2025) A two-step regulatory mechanism dynamically controls histone H3 acetylation by SAGA complex at growth-related promoters. Nucleic Acids Res 53(7)

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Abstract


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 relationship between H3K9ac and gene expression remains mostly correlative. In this study, we identify a large suite of growth-related (GR) genes in yeast that undergo a particularly strong down-regulation of both transcription and promoter-associated H3K9ac upon stress, and delineate the roles of transcriptional activators (TAs), repressors, SAGA (Spt-Ada-Gcn5 acetyltransferase) 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 (TRs) and activators, that is independent of transcription. In response to stress, promoter release of TAs at GR genes is a prerequisite for rapid reduction of H3K9ac, whereas binding of TRs is required to establish a hypo-acetylated, strongly repressed state.

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Journal Article
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Zencir S, Dilg D, Bruzzone MJ, Stutz F, Soudet J, Shore D, Albert B
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