The yeast Cyc8–Tup1 complex cooperates with Hda1p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FLO1 gene

• Published in: Biochimica et biophysica acta Vol. 1839; no. 11; pp. 1242 - 1255
• Main Authors: Fleming, Alastair B., Beggs, Suzanne, Church, Michael, Tsukihashi, Yoshihiro, Pennings, Sari
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2014; Elsevier
• Subjects: Chromatin; Cyc8 (Ssn6)-Tup1; Down-Regulation - genetics; Gene Expression Regulation, Fungal; Gene repression; Histone acetylation; Histone Deacetylases - metabolism; Mannose-Binding Lectins - genetics; Mannose-Binding Lectins - metabolism; Nuclear Proteins - metabolism; Nuclear Proteins - physiology; Organisms, Genetically Modified; Protein Binding; Repressor Proteins - metabolism; Repressor Proteins - physiology; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Saccharomyces cerevisiae Proteins - physiology; Swi–Snf; Telomere - metabolism; Transcription, Genetic; Cyc8 (Ssn6)-Tup1; Chromatin; Histone acetylation; Gene repression; Saccharomyces cerevisiae; Swi–Snf
• ISSN: 1874-9399; 0006-3002; 1876-4320
• DOI: 10.1016/j.bbagrm.2014.07.022

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. •Cyc8–Tup1 repression activity is enriched at chromosome subtelomeric regions.•The subtelomeric FLO1 gene is subject to chromatin-mediated repression by Cyc8–Tup1.•Cyc8–Tup1 promotes long-range nucleosome positioning and histone deacetylation.•Hda1p and Rpd3p cooperate with Cyc8–Tup1 to facilitate this repressive chromatin.•Swi–Snf directs extensive nucleosome remodelling when Cyc8–Tup1 is absent.