Sas3 and Ada2(Gcn5)-dependent histone H3 acetylation is required for transcription elongation at the de-repressed FLO1 gene

The S. cerevisiae FLO1 gene encodes a cell wall protein that imparts cell-cell adhesion. FLO1transcription is regulated via the antagonistic activities of the Tup1-Cyc8 co-repressor and Swi-Snfco-activator complexes. Tup1-Cyc8 represses transcription through the organisation of stronglypositioned, hypoacetylated nucleosomes across gene promoters. Swi-Snf catalyses remodelling ofthese nucleosomes in a mechanism involving histone acetylation that is poorly understood. Here,we show that FLO1 de-repression is accompanied by Swi-Snf recruitment, promoter histone eviction,and Sas3 and Ada2(Gcn5)-dependent histone H3K14 acetylation. In the absence of H3K14acetylation, Swi-Snf recruitment and histone eviction proceed, but transcription is reduced,suggesting these processes, while essential, are not sufficient for de-repression. Further analysis inthe absence of H3K14 acetylation reveals RNAP II recruitment at the FLO1 promoter still occurs, butRNAP II is absent from the gene-coding region, demonstrating Sas3 and Ada2-dependent histone H3acetylation is required for transcription elongation. Analysis of the transcription kinetics at othergenes reveals shared mechanisms coupled to a distinct role for histone H3 acetylation, essential atFLO1, downstream of initiation. We propose histone H3 acetylation in the coding region providesrate-limiting control during the transition from initiation to elongation which dictates whether thegene is permissive for transcription.