title: SWI/SNF binding to the HO promoter requires histone acetylation and stimulates TATA-binding protein recruitment.
abstract: We use chromatin immunoprecipitation assays to show that the Gcn5 histone acetyltransferase in SAGA is required for SWI/SNF association with the HO promoter and that binding of SWI/SNF and SAGA are interdependent. Previous results showed that SWI/SNF binding to HO was Gcn5 independent, but that work used a strain with a mutation in the Ash1 daughter-specific repressor of HO expression. Here, we show that Ash1 functions as a repressor that inhibits SWI/SNF binding and that Gcn5 is required to overcome Ash1 repression in mother cells to allow HO transcription. Thus, Gcn5 facilitates SWI/SNF binding by antagonizing Ash1. Similarly, a mutation in SIN3, like an ash1 mutation, allows both HO expression and SWI/SNF binding in the absence of Gcn5. Although Ash1 has recently been identified in a Sin3-Rpd3 complex, our genetic analysis shows that Ash1 and Sin3 have distinct functions in regulating HO. Analysis of mutant strains shows that SWI/SNF binding and HO expression are correlated and regulated by histone acetylation. The defect in HO expression caused by a mutant SWI/SNF with a Swi2(E834K) substitution can be partially suppressed by ash1 or spt3 mutation or by a gain-of-function V71E substitution in the TATA-binding protein (TBP). Spt3 inhibits TBP binding at HO, and genetic analysis suggests that Spt3 and TBP(V71E) act in the same pathway, distinct from that of Ash1. We have detected SWI/SNF binding at the HO TATA region, and our results suggest that SWI/SNF, either directly or indirectly, facilitates TBP binding at HO.
authors.affiliation: Department of Pathology, University of Utah, 15 North Medical Drive East, Salt Lake City, UT 84132-2501, USA.
authors.forename: Doyel
authors.initials: D
authors.lastname: Mitra
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Parnell
authors.forename: Jack W
authors.initials: JW
authors.lastname: Landon
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Yu
authors.forename: David J
authors.initials: DJ
authors.lastname: Stillman
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases; D000483:Alleles; D002384:Catalysis; D018797:Cell Cycle Proteins / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics*; D005656:Fungal Proteins / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors; D006655:Histone Deacetylases; D006657:Histones / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013489:Suppression, Genetic; D035181:TATA-Box Binding Protein / Q000378:metabolism*; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D015252:Deoxyribonucleases, Type II Site-Specific; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D006657:Histones; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; C098733:ASH1 protein, S cerevisiae; C071731:SIN3 protein, S cerevisiae; C445179:SWI-SNF-B chromatin-remodeling complex; C080218:SWI5 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C530845:HO protein, S cerevisiae; C037725:SCEI protein, S cerevisiae; C499333:SNF2 protein, S cerevisiae