Reciprocal nuclear shuttling of two antagonizing Zn finger proteins modulates Tup family corepressor function to repress chromatin remodeling.
The Schizosaccharomyces pombe global corepressors Tup11 and Tup12, which are orthologs of Saccharomyces cerevisiae Tup1, are involved in glucose-dependent transcriptional repression and chromatin alteration of the fbp1+ gene. The fbp1+ promoter contains two regulatory elements, UAS1 and UAS2, one of which (UAS2) serves as a binding site for two antagonizing C2H2 Zn finger transcription factors, the Rst2 activator and the Scr1 repressor. In this study, we analyzed the role of Tup proteins and Scr1 in chromatin remodeling at fbp1+ during glucose repression. We found that Scr1, cooperating with Tup11 and Tup12, functions to maintain the chromatin of the fbp1+ promoter in a transcriptionally inactive state under glucose-rich conditions. Consistent with this notion, Scr1 is quickly exported from the nucleus to the cytoplasm at the initial stage of derepression, immediately after glucose starvation, at which time Rst2 is known to be imported into the nucleus. In addition, chromatin immunoprecipitation assays revealed a switching of Scr1 to Rst2 bound at UAS2 during glucose derepression. On the other hand, Tup11 and Tup12 persist in the nucleus and bind to the fbp1+ promoter under both derepressed and repressed conditions. These observations suggest that Tup1-like proteins recruited to the fbp1+ promoter are controlled by either of two antagonizing C2H2 Zn finger proteins. We propose that the actions of Tup11 and Tup12 are regulated by reciprocal nuclear shuttling of the two antagonizing Zn finger proteins in response to the extracellular glucose concentration. This notion provides new insights into the molecular mechanisms of the Tup family corepressors in gene regulation.
Hirota
Kouji
K
Genetic System Regulation Laboratory, RIKEN (The Institute of Physical and Chemical Research), Discovery Research Institute, Wako-shi, Saitama 351-0198, Japan. khirota@riken.jp
Hoffman
Charles S
CS
Ohta
Kunihiro
K
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D001483:Base Sequence; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D006597:Fructose-Bisphosphatase; D005800:Genes, Fungal; D008954:Models, Biological; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D016335:Zinc Fingers / Q000235:genetics
D004271:DNA, Fungal; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C471691:Tup11 protein, S pombe; C471692:Tup12 protein, S pombe; C111172:FBP1 protein, S cerevisiae; D006597:Fructose-Bisphosphatase; D009699:N-Glycosyl Hydrolases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C101825:NTG1 protein, S cerevisiae