Zencir Sevil, Dilg Daniel, Bruzzone Maria Jessica, Stutz Françoise, Soudet Julien, Shore David, Albert Benjamin
Department of Molecular and Cellular Biology, Université de Genève, 1211, Geneva, Switzerland.
Nucleic Acids Res. 2025 Apr 10;53(7). doi: 10.1093/nar/gkaf276.
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.
组蛋白H3第9位赖氨酸残基的乙酰化（H3K9ac）是一种动态调控的标记，与真核生物中转录活跃的启动子相关。然而，我们对H3K9ac与基因表达之间关系的理解大多仍停留在相关性层面。在本研究中，我们鉴定出酵母中一大类与生长相关（GR）的基因，这些基因在应激时转录和启动子相关的H3K9ac均会发生特别强烈的下调，并阐明了转录激活因子（TAs）、阻遏因子、SAGA（Spt-Ada-Gcn5乙酰转移酶）组蛋白乙酰转移酶和RNA聚合酶II在此反应中的作用。我们证明，H3K9的乙酰化状态由转录阻遏因子（TRs）和激活因子的动态结合驱动的两步机制所调控，该机制独立于转录过程。在应激反应中，GR基因处TA从启动子上的释放是H3K9ac快速减少的先决条件，而TRs的结合则是建立低乙酰化、强抑制状态所必需的。
