The yeast Cyc8-Tupl complex cooperates with Hdal p and Rpd3p histone deacetylases to robustly repress transcription of the subtelomeric FL01 gene

摘要

We demonstrate that the yeast flocculation gene, KOI, is representative of a distinct subset of subtelomeric genes that are robustly repressed by the Cyc8-Tupl complex. We have examined Cyc8-Tupl localisation, histone acetylation and long-range chromatin remodelling within the extensive FL01 upstream region. We show that Cyc8-Tupl is localised in a DNase I hypersensitive site within an ordered array of strongly positioned nucleo-somes around -700 base pairs upstream of the transcription start site. In cyc8 deletion mutant strains, Tuplp localisation is absent, with concomitant histone hyperacetylation of adjacent regions at the FL01 promoter. This is accompanied by extensive histone depletion across the upstream region and gene activation. The yeast. histone deacetylases, Hdalp and Rpd3p, occupy the repressed FL01 promoter region in a Cyc8-Tupl dependent manner and coordinate histone deacetylation, nudeosome stabilisation and gene repression. Moreover, we show that the ATP-dependent chromatin remodelling complex Swi-Snf occupies the site vacated by Cyc8-Tupl in a cyc8 mutant. These data suggest that distinctly bound Cyc8-Tupl cooperates with Hdalp and Rpd3p to establish or maintain an extensive array of strongly positioned, deacetylated nucleosomes over the FL01 promoter and upstream region which inhibit histone acetylation, block Swi-Snf binding and prevent transcription.