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Molecular and Cellular Biology, January 2003, p. 677-686, Vol. 23, No. 2
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.2.677-686.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Transcription Factor Rim101p Governs Ion Tolerance and Cell Differentiation by Direct Repression of the Regulatory Genes NRG1 and SMP1 in Saccharomyces cerevisiae

Teresa M. Lamb and Aaron P. Mitchell*

Department of Microbiology and Institute of Cancer Research, Columbia University, New York, New York 10032

Received 6 September 2002/ Returned for modification 15 October 2002/ Accepted 29 October 2002

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 rim101{Delta} 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.


* Corresponding author. Mailing address: Department of Microbiology, Columbia University, 701 West 168th St., New York, NY 10032. Phone: (212) 305-8251. Fax: (212) 305-1741. E-mail: apm4{at}columbia.edu.


Molecular and Cellular Biology, January 2003, p. 677-686, Vol. 23, No. 2
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.2.677-686.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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