Recruitment of the yeast Tup1p-Ssn6p repressor is associated with localized decreases in histone acetylation

Posttranslational acetylation of histones is an important element of transc riptional regulation. The yeast Tup1p repressor is one of only a few non-en zyme proteins known to interact directly with the amino-terminal tail domai ns of histones H3 and H4 that are subject to acetylation. We demonstrated p reviously that Tup1p interacts poorly with more highly acetylated isoforms of these histones in vitro. Here we show that two separate classes of promo ters repressed by Tup1p are associated with underacetylated histones in viv o. This decreased histone acetylation is dependent upon Tup1p and its partn er Ssn6p and is localized to sequences near the point of Tup1p-Ssn6p recrui tment. Increased acetylation of histones H3 and H4 is observed upon activat ion of these genes, but this increase is not dependent on transcription per se. Direct recruitment of Tup1p-Ssn6p complexes via fusion of Tup1p to the lexA DNA binding domain is sufficient to confer repression and induce decr eased acetylation of H3 and H4 at a target promoter. Taken together, our re sults suggest that stable decreases in histone acetylation levels are direc ted and/or maintained by the Tup1p-Ssn6p repressor complex.