Antagonistic Controls of Chromatin and mRNA Start Site Selection by Tup Family Corepressors and the CCAAT-Binding Factor

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. TheSchizosaccharomyces pombe fission yeast Tup family corepressors Tup11 and Tup12 (Tup11/12), which are orthologs of Tup1 inSaccharomyces cerevisiae budding yeast and Groucho inDrosophila , 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 thefbp1 + promoter region where the Atf1 and Rst2 transcriptional activators bind. Second, they repress the formation of an open chromatin configuration at thefbp1 + TATA box. Third, they repress mRNA transcriptionper 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, C2 H2 zinc finger-type Rst2, and CBF/NF-Y-type Php5 proteins. We also found that impaired chromatin remodeling andfbp1 + mRNA transcription inphp5 Δ strains are rescued by the double deletions oftup11 + andtup12 + , 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.