title: The yeast Cyc8-Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene.
abstract: We demonstrate that the yeast flocculation gene, FLO1, is representative of a distinct subset of subtelomeric genes that are robustly repressed by the Cyc8-Tup1 complex. We have examined Cyc8-Tup1 localisation, histone acetylation and long-range chromatin remodelling within the extensive FLO1 upstream region. We show that Cyc8-Tup1 is localised in a DNase I hypersensitive site within an ordered array of strongly positioned nucleosomes around -700 base pairs upstream of the transcription start site. In cyc8 deletion mutant strains, Tup1p localisation is absent, with concomitant histone hyperacetylation of adjacent regions at the FLO1 promoter. This is accompanied by extensive histone depletion across the upstream region and gene activation. The yeast histone deacetylases, Hda1p and Rpd3p, occupy the repressed FLO1 promoter region in a Cyc8-Tup1 dependent manner and coordinate histone deacetylation, nucleosome stabilisation and gene repression. Moreover, we show that the ATP-dependent chromatin remodelling complex Swi-Snf occupies the site vacated by Cyc8-Tup1 in a cyc8 mutant. These data suggest that distinctly bound Cyc8-Tup1 cooperates with Hda1p and Rpd3p to establish or maintain an extensive array of strongly positioned, deacetylated nucleosomes over the FLO1 promoter and upstream region which inhibit histone acetylation, block Swi-Snf binding and prevent transcription.
authors.affiliation: School of Genetics and Microbiology, Trinity College Dublin, College Green, Dublin 2, Ireland; School of Biomedical Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK. Electronic address: alastair.fleming@tcd.ie.
authors.forename: Alastair B
authors.initials: AB
authors.lastname: Fleming
authors.affiliation: School of Genetics and Microbiology, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Beggs
authors.affiliation: School of Genetics and Microbiology, Trinity College Dublin, College Green, Dublin 2, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Church
authors.affiliation: School of Biomedical Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tsukihashi
authors.affiliation: School of Biomedical Sciences, University of Edinburgh, Edinburgh, EH8 9XD, UK; Queen's Medical Research Institute, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
authors.forename: Sari
authors.initials: S
authors.lastname: Pennings
mesh_terms: D015536:Down-Regulation / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases / Q000378:metabolism*; D037241:Mannose-Binding Lectins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D030781:Organisms, Genetically Modified; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D016615:Telomere / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C065455:CYC8 protein, S cerevisiae; C087578:FLO1 protein, S cerevisiae; D037241:Mannose-Binding Lectins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; C499673:HDA1 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases
keywords: Chromatin; Cyc8 (Ssn6)-Tup1; Gene repression; Histone acetylation; Saccharomyces cerevisiae; Swi–Snf
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