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Eukaryotic Cell, February 2004, p. 221-231, Vol. 3, No. 1
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.1.221-231.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Regulatory Network Connecting Two Glucose Signal Transduction Pathways in Saccharomyces cerevisiae{dagger}

Aneta Kaniak,1 Zhixiong Xue,2 Daniel Macool,2 Jeong-Ho Kim,1 and Mark Johnston1*

Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110,1 DuPont Central Research, Experimental Station, Wilmington, Delaware 19880-01732

Received 26 September 2003/ Accepted 10 November 2003

The yeast Saccharomyces cerevisiae senses glucose, its preferred carbon source, through multiple signal transduction pathways. In one pathway, glucose represses the expression of many genes through the Mig1 transcriptional repressor, which is regulated by the Snf1 protein kinase. In another pathway, glucose induces the expression of HXT genes encoding glucose transporters through two glucose sensors on the cell surface that generate an intracellular signal that affects function of the Rgt1 transcription factor. We profiled the yeast transcriptome to determine the range of genes targeted by this second pathway. Candidate target genes were verified by testing for Rgt1 binding to their promoters by chromatin immunoprecipitation and by measuring the regulation of the expression of promoter lacZ fusions. Relatively few genes could be validated as targets of this pathway, suggesting that this pathway is primarily dedicated to regulating the expression of HXT genes. Among the genes regulated by this glucose signaling pathway are several genes involved in the glucose induction and glucose repression pathways. The Snf3/Rgt2-Rgt1 glucose induction pathway contributes to glucose repression by inducing the transcription of MIG2, which encodes a repressor of glucose-repressed genes, and regulates itself by inducing the expression of STD1, which encodes a regulator of the Rgt1 transcription factor. The Snf1-Mig1 glucose repression pathway contributes to glucose induction by repressing the expression of SNF3 and MTH1, which encodes another regulator of Rgt1, and also regulates itself by repressing the transcription of MIG1. Thus, these two glucose signaling pathways are intertwined in a regulatory network that serves to integrate the different glucose signals operating in these two pathways.

* Corresponding author. Mailing address: Department of Genetics, Campus Box 8232, Washington University Medical School, 4566 Scott Ave., St. Louis, MO 63110. Phone: (314) 362-2735. Fax: (314) 362-7855. E-mail: mj{at}genetics.wustl.edu.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.

Eukaryotic Cell, February 2004, p. 221-231, Vol. 3, No. 1
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.1.221-231.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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