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.
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.
Mesh Terms:
Cell Cycle Proteins, Cross-Linking Reagents, DNA, DNA-Binding Proteins, Gene Expression Regulation, Genotype, Glucose, Immunoblotting, Immunoprecipitation, Models, Biological, Mutation, Nucleic Acid Hybridization, Phosphoprotein Phosphatases, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Phosphatase 1, Protein Processing, Post-Translational, RNA, Messenger, Ribonucleases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Time Factors, Transcription Factor TFIID, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Two-Hybrid System Techniques
Cell Cycle Proteins, Cross-Linking Reagents, DNA, DNA-Binding Proteins, Gene Expression Regulation, Genotype, Glucose, Immunoblotting, Immunoprecipitation, Models, Biological, Mutation, Nucleic Acid Hybridization, Phosphoprotein Phosphatases, Plasmids, Promoter Regions, Genetic, Protein Binding, Protein Phosphatase 1, Protein Processing, Post-Translational, RNA, Messenger, Ribonucleases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Time Factors, Transcription Factor TFIID, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Two-Hybrid System Techniques
Mol. Cell. Biol.
Date: Jan. 01, 2005
PubMed ID: 15601868
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