Regulation of Gluconeogenesis in Saccharomyces cerevisiae Is Mediated by Activator and Repressor Functions of Rds2

Author:

Soontorngun Nitnipa1,Larochelle Marc2,Drouin Simon3,Robert François3,Turcotte Bernard214

Affiliation:

1. Biochemistry

2. Departments of Medicine

3. Institut de Recherches Cliniques de Montréal, Montréal, Québec, Canada H2W 1R7

4. Microbiology and Immunology, Royal Victoria Hospital, McGill University, Montréal, Québec, Canada H3A 1A1

Abstract

ABSTRACT In Saccharomyces cerevisiae , RDS2 encodes a zinc cluster transcription factor with unknown function. Here, we unravel a key function of Rds2 in gluconeogenesis using chromatin immunoprecipitation-chip technology. While we observed that Rds2 binds to only a few promoters in glucose-containing medium, it binds many additional genes when the medium is shifted to ethanol, a nonfermentable carbon source. Interestingly, many of these genes are involved in gluconeogenesis, the tricarboxylic acid cycle, and the glyoxylate cycle. Importantly, we show that Rds2 has a dual function: it directly activates the expression of gluconeogenic structural genes while it represses the expression of negative regulators of this pathway. We also show that the purified DNA binding domain of Rds2 binds in vitro to carbon source response elements found in the promoters of target genes. Finally, we show that upon a shift to ethanol, Rds2 activation is correlated with its hyperphosphorylation by the Snf1 kinase. In summary, we have characterized Rds2 as a novel major regulator of gluconeogenesis.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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