title: Chd1 and yFACT act in opposition in regulating transcription.
abstract: CHD1 encodes an ATP-dependent chromatin remodeler with two chromodomains. Deletion of CHD1 suppresses the temperature-sensitive growth defect caused by mutations in either SPT16 or POB3, which encode subunits of the yFACT chromatin-reorganizing complex. chd1 also suppresses synthetic defects caused by combining an spt16 mutation with other transcription factor mutations, including the synthetic lethality caused by combining an spt16 mutation with TATA binding protein (TBP) or TFIIA defects. Binding of TBP and RNA polymerase II to the GAL1 promoter is reduced in a pob3 mutant, resulting in low levels of GAL1 expression, and all three defects are suppressed by removing Chd1. These results suggest that Chd1 and yFACT have opposing roles in regulating TBP binding at promoters. Additionally, overexpression of Chd1 is tolerated in wild-type cells but is toxic in spt16 mutants. Further, both the ATPase and chromodomain are required for Chd1 activity in opposing yFACT function. Similar to the suppression by chd1, mutations in the SET2 histone methyltransferase also suppress defects caused by yFACT mutations. chd1 and set2 are additive in suppressing pob3, suggesting that Chd1 and Set2 act in distinct pathways. Although human Chd1 has been shown to bind to H3-K4-Me, we discuss evidence arguing that yeast Chd1 binds to neither H3-K4-Me nor H3-K36-Me.
authors.affiliation: Department of Pathology, University of Utah, 15 N. Medical Drive East, Salt Lake City, UT 84112, USA.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Biswas
authors.forename: Rinku
authors.initials: R
authors.lastname: Dutta-Biswas
authors.forename: David J
authors.initials: DJ
authors.lastname: Stillman
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D035181:TATA-Box Binding Protein / Q000378:metabolism; D035561:Transcription Factor TFIIA / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors
chemical_list: C489847:CHD1 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C106768:POB3 protein, S cerevisiae; C071238:SPT16 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein; D035561:Transcription Factor TFIIA; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors