title: Sas3 and Ada2(Gcn5)-dependent histone H3 acetylation is required for transcription elongation at the de-repressed FLO1 gene.
abstract: 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.
authors.affiliation: School of Genetics and Microbiology, University of Dublin, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Church
authors.affiliation: School of Genetics and Microbiology, University of Dublin, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Kim C
authors.initials: KC
authors.lastname: Smith
authors.affiliation: School of Genetics and Microbiology, University of Dublin, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Alhussain
authors.affiliation: Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
authors.forename: Sari
authors.initials: S
authors.lastname: Pennings
authors.affiliation: School of Genetics and Microbiology, University of Dublin, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Alastair B
authors.initials: AB
authors.lastname: Fleming
mesh_terms: D000107:Acetylation; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D061805:Transcription Elongation, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: C090575:ADA2 protein, S cerevisiae; C065455:CYC8 protein, S cerevisiae; D002868:Chromosomal Proteins, Non-Histone; C087578:FLO1 protein, S cerevisiae; D006657:Histones; D037241:Mannose-Binding Lectins; D009687:Nuclear Proteins; D009707:Nucleosomes; D012097:Repressor Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C526757:SAS3 protein, S cerevisiae; D012319:RNA Polymerase II