title: 14-3-3 (Bmh) proteins regulate combinatorial transcription following RNA polymerase II recruitment by binding at Adr1-dependent promoters in Saccharomyces cerevisiae.
abstract: Adr1 and Cat8 are nutrient-regulated transcription factors in Saccharomyces cerevisiae that coactivate genes necessary for growth in the absence of a fermentable carbon source. Transcriptional activation by Adr1 is dependent on the AMP-activated protein kinase Snf1 and is inhibited by binding of Bmh, yeast 14-3-3 proteins, to the phosphorylated Adr1 regulatory domain. We show here that Bmh inhibits transcription by binding to Adr1 at promoters that contain a preinitiation complex, demonstrating that Bmh-mediated inhibition is not due to nuclear exclusion, inhibition of DNA binding, or RNA polymerase II (Pol II) recruitment. Adr1-dependent mRNA levels under repressing growth conditions are synergistically enhanced in a mutant lacking Bmh and the two major histone deacetylases (HDACs), suggesting that Bmh and HDACs inhibit gene expression independently. The synergism requires Snf1 and Adr1 but not Cat8. Inactivating Bmh or preventing it from binding to Adr1 suppresses the normal requirement for Cat8 at codependent promoters, suggesting that Bmh modulates combinatorial control of gene expression in addition to having an inhibitory role in transcription. Activating Snf1 by deleting Reg1, a Glc7 protein phosphatase regulatory subunit, is lethal in combination with defective Bmh in strain W303, suggesting that Bmh and Snf1 have opposing roles in an essential cellular process.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Braun
authors.forename: Pabitra K
authors.initials: PK
authors.lastname: Parua
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Dombek
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Miner
authors.forename: Elton T
authors.initials: ET
authors.lastname: Young
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D048948:14-3-3 Proteins; C074682:ADR1 protein, S cerevisiae; C075852:BMH1 protein, S cerevisiae; C097164:BMH2 protein, S cerevisiae; C092600:CAT8 protein, S cerevisiae; D004268:DNA-Binding Proteins; C052130:GAL4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II; D006655:Histone Deacetylases