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

• Published in: Nucleic acids research Vol. 45; no. 8; pp. gkx028 - 4430
• Main Authors: Church, Michael, Smith, Kim C., Alhussain, Mohamed M., Pennings, Sari, Fleming, Alastair B.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 05.05.2017
• Subjects: Acetylation; Cell Wall - genetics; Cell Wall - metabolism; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Gene Expression Regulation, Fungal; Gene regulation, Chromatin and Epigenetics; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Histones - genetics; Histones - metabolism; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nucleosomes - chemistry; Nucleosomes - metabolism; Promoter Regions, Genetic; Protein Binding; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Transcription Elongation, Genetic; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkx028

The Saccharomyces cerevisiae FLO1 gene encodes a cell wall protein that imparts cell-cell adhesion. FLO1 transcription is regulated via the antagonistic activities of the Tup1-Cyc8 co-repressor and Swi-Snf co-activator complexes. Tup1-Cyc8 represses transcription through the organization of strongly positioned, hypoacetylated nucleosomes across gene promoters. Swi-Snf catalyzes remodeling of these 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 H3K14 acetylation, Swi-Snf recruitment and histone eviction proceed, but transcription is reduced, suggesting these processes, while essential, are not sufficient for de-repression. Further analysis in the absence of H3K14 acetylation reveals RNAP II recruitment at the FLO1 promoter still occurs, but RNAP II is absent from the gene-coding region, demonstrating Sas3 and Ada2-dependent histone H3 acetylation is required for transcription elongation. Analysis of the transcription kinetics at other genes reveals shared mechanisms coupled to a distinct role for histone H3 acetylation, essential at FLO1, downstream of initiation. We propose histone H3 acetylation in the coding region provides rate-limiting control during the transition from initiation to elongation which dictates whether the gene is permissive for transcription.