title: Antagonistic controls of chromatin and mRNA start site selection by Tup family corepressors and the CCAAT-binding factor.
abstract: The Tup family corepressors contribute to critical cellular responses, such as the stress response and differentiation, presumably by inducing repressive chromatin, though the precise repression mechanism remains to be elucidated. The Schizosaccharomyces pombe fission yeast Tup family corepressors Tup11 and Tup12 (Tup11/12), which are orthologs of Tup1 in Saccharomyces cerevisiae budding yeast and Groucho in Drosophila, negatively control chromatin and the transcriptional activity of some stress-responsive genes. Here, we demonstrate that Tup11/12 repress transcription of a gluconeogenesis gene, fbp1⁺, by three distinct mechanisms. First, Tup11/12 inhibit chromatin remodeling in the fbp1⁺ promoter region where the Atf1 and Rst2 transcriptional activators bind. Second, they repress the formation of an open chromatin configuration at the fbp1⁺ TATA box. Third, they repress mRNA transcription per se by regulating basic transcription factors. These inhibitory actions of Tup11/12 are antagonized by three different types of transcriptional activators: CREB/ATF-type Atf1, C₂H₂zinc finger-type Rst2, and CBF/NF-Y-type Php5 proteins. We also found that impaired chromatin remodeling and fbp1⁺ mRNA transcription in php5Δ strains are rescued by the double deletions of tup11⁺ and tup12⁺, although the distribution of the transcription start sites becomes broader than that in wild-type cells. These data reveal a new mechanism of precise determination of the mRNA start site by Tup family corepressors and CBF/NF-Y proteins.
authors.affiliation: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Tokyo, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Asada
authors.affiliation: Department of Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Takemata
authors.affiliation: Biology Department, Boston College, Chestnut Hill, Massachusetts, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Hoffman
authors.affiliation: Department of Life Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, Tokyo, Japan khirota@tmu.ac.jp.
authors.forename: Kouji
authors.initials: K
authors.lastname: Hirota
mesh_terms: D000818:Animals; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004330:Drosophila; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D024363:Transcription Initiation Site
chemical_list: D023081:CCAAT-Binding Factor; D002843:Chromatin; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C066502:TUP1 protein, S cerevisiae; C471690:TUP1 protein, S pombe