title: The transcription factor Rim101p governs ion tolerance and cell differentiation by direct repression of the regulatory genes NRG1 and SMP1 in Saccharomyces cerevisiae.
abstract: Environmental pH changes have broad consequences for growth and differentiation. The best-understood eukaryotic pH response pathway acts through the zinc-finger transcription factor PacC of Aspergillus nidulans, which activates alkaline pH-induced genes directly. We show here that Saccharomyces cerevisiae Rim101p, the pH response regulator homologous to PacC, functions as a repressor in vivo. Chromatin immunoprecipitation assays show that Rim101p is associated in vivo with the promoters of seven Rim101p-repressed genes. A reporter gene containing deduced Rim101p binding sites is negatively regulated by Rim101p and is associated with Rim101p in vivo. Deletion mutations of the Rim101p repression targets NRG1 and SMP1 suppress rim101Delta mutant defects in ion tolerance, haploid invasive growth, and sporulation. Therefore, transcriptional repression is the main biological function of Rim101p. The Rim101p repression target Nrg1p is in turn required for repression of two alkaline pH-inducible genes, including the Na+ pump gene ENA1, which is required for ion tolerance. Thus, Nrg1p, a known transcriptional repressor, functions as an inhibitor of alkaline pH responses. Our findings stand in contrast to the well-characterized function of PacC as a direct activator of alkaline pH-induced genes yet explain many aspects of Rim101p and PacC function in other organisms.
authors.affiliation: Department of Microbiology and Institute of Cancer Research, Columbia University, New York, New York 10032, USA. apm4@columbia.edu
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Lamb
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Mitchell
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D015152:Blotting, Northern; D027682:Cation Transport Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism* / Q000502:physiology*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D006863:Hydrogen-Ion Concentration; D007763:Lac Operon; D008954:Models, Biological; D020890:Neuregulin-1 / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D011233:Precipitin Tests; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase; D014157:Transcription Factors / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; C086375:ENA1 protein, S cerevisiae; D005656:Fungal Proteins; D020890:Neuregulin-1; D009687:Nuclear Proteins; C092394:PacC protein, Aspergillus; C489601:RIM101 protein, S cerevisiae; D012097:Repressor Proteins; C470554:SMP1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C066502:TUP1 protein, S cerevisiae; D014157:Transcription Factors; D011061:Poly A; D012965:Sodium Chloride; D012964:Sodium; D001616:beta-Galactosidase; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase