title: The Ccr4-Not complex independently controls both Msn2-dependent transcriptional activation--via a newly identified Glc7/Bud14 type I protein phosphatase module--and TFIID promoter distribution.
abstract: The Ccr4-Not complex is a conserved global regulator of gene expression, which serves as a regulatory platform that senses and/or transmits nutrient and stress signals to various downstream effectors. Presumed effectors of this complex in yeast are TFIID, a general transcription factor that associates with the core promoter, and Msn2, a key transcription factor that regulates expression of stress-responsive element (STRE)-controlled genes. Here we show that the constitutively high level of STRE-driven expression in ccr4-not mutants results from two independent effects. Accordingly, loss of Ccr4-Not function causes a dramatic Msn2-independent redistribution of TFIID on promoters with a particular bias for STRE-controlled over ribosomal protein gene promoters. In parallel, loss of Ccr4-Not complex function results in an alteration of the posttranslational modification status of Msn2, which depends on the type 1 protein phosphatase Glc7 and its newly identified subunit Bud14. Tests of epistasis as well as transcriptional analyses of Bud14-dependent transcription support a model in which the Ccr4-Not complex prevents activation of Msn2 via inhibition of the Bud14/Glc7 module in exponentially growing cells. Thus, increased activity of STRE genes in ccr4-not mutants may result from both altered general distribution of TFIID and unscheduled activation of Msn2.
authors.affiliation: Département de Microbiologie et Médecine Moléculaire, CMU, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Eve
authors.initials: E
authors.lastname: Lenssen
authors.forename: Nicole
authors.initials: N
authors.lastname: James
authors.forename: Ivo
authors.initials: I
authors.lastname: Pedruzzi
authors.forename: Frédérique
authors.initials: F
authors.lastname: Dubouloz
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cameroni
authors.forename: Ruth
authors.initials: R
authors.lastname: Bisig
authors.forename: Laurent
authors.initials: L
authors.lastname: Maillet
authors.forename: Michel
authors.initials: M
authors.lastname: Werner
authors.forename: Johnny
authors.initials: J
authors.lastname: Roosen
authors.forename: Katarina
authors.initials: K
authors.lastname: Petrovic
authors.forename: Joris
authors.initials: J
authors.lastname: Winderickx
authors.forename: Martine A
authors.initials: MA
authors.lastname: Collart
authors.forename: Claudio
authors.initials: C
authors.lastname: De Virgilio
mesh_terms: D018797:Cell Cycle Proteins / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D008954:Models, Biological; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054645:Protein Phosphatase 1; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D012260:Ribonucleases / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D035362:Transcription Factor TFIID / Q000737:chemistry; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: C474555:Bud14 protein, S cerevisiae; C079592:CDC39 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; C081935:MSN2 protein, S cerevisiae; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D035362:Transcription Factor TFIID; D014157:Transcription Factors; D004247:DNA; C078657:CCR4 protein, S cerevisiae; D012260:Ribonucleases; C092048:GLC7 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D005947:Glucose