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Grigat, M, Jäschke, Y, Kliewe, F, Pfeifer, M, Walz, S and Schüller, HJ (2012) Multiple histone deacetylases are recruited by corepressor Sin3 and contribute to gene repression mediated by Opi1 regulator of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae. Mol. Genet. Genomics 287:461-72

Yeast genes of phospholipid biosynthesis are negatively regulated by repressor protein Opi1 when precursor molecules inositol and choline (IC) are available. Opi1-triggered gene repression is mediated by recruitment of the Sin3 corepressor complex. In this study, we systematically investigated the regulatory contribution of subunits of Sin3 complexes and identified Pho23 as important for IC-dependent gene repression. Two non-overlapping regions within Pho23 mediate its direct interaction with Sin3. Previous work has shown that Sin3 recruits the histone deacetylase (HDAC) Rpd3 to execute gene repression. While deletion of SIN3 strongly alleviates gene repression by IC, an rpd3 null mutant shows almost normal regulation. We thus hypothesized that various HDACs may contribute to Sin3-mediated repression of IC-regulated genes. Indeed, a triple mutant lacking HDACs, Rpd3, Hda1 and Hos1, could phenocopy a sin3 single mutant. We show that these proteins are able to contact Sin3 in vitro and in vivo and mapped three distinct HDAC interaction domains, designated HID1, HID2 and HID3. HID3, which is identical to the previously described structural motif PAH4 (paired amphipathic helix), can bind all HDACs tested. Chromatin immunoprecipitation studies finally confirmed that Hda1 and Hos1 are recruited to promoters of phospholipid biosynthetic genes INO1 and CHO2.

PubMed Online version:10.1007/s00438-012-0692-x

Amino Acid Sequence; Gene Expression Regulation, Fungal; Genes, Fungal; Histone Deacetylases/chemistry; Histone Deacetylases/genetics; Histone Deacetylases/metabolism; Molecular Sequence Data; Mutation; Nuclear Proteins/chemistry; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phospholipids/biosynthesis; Protein Interaction Domains and Motifs; Repressor Proteins/chemistry; Repressor Proteins/genetics; Repressor Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Saccharomyces cerevisiae Proteins/chemistry; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Sequence Homology, Amino Acid; Sin3 Histone Deacetylase and Corepressor Complex/chemistry; Sin3 Histone Deacetylase and Corepressor Complex/genetics; Sin3 Histone Deacetylase and Corepressor Complex/metabolism