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Natural variation in the yeast glucose-signaling network reveals a new role for the Mig3p transcription factor

ABSTRACT: The Crabtree effect, in which fermentative metabolism is preferred at the expense of respiration, is a hallmark of budding yeast’s glucose response and a model for the Warburg effect in human tumors. While the glucose-responsive transcriptional repressors Mig1p and Mig2p play well-characterized roles in the Crabtree effect, little function for the related Mig3p transcription factor has been uncovered despite numerous investigations of laboratory yeast strains. Here we studied a wild isolate of Saccharomyces cerevisiae to uncover a critical role for Mig3p that has been lost in S288c-derived laboratory strains. We found that Mig3p affects the expression of hundreds of glucose-responsive genes in the oak strain YPS163, both during growth under standard conditions and upon ethanol treatment. Our results suggest that Mig3p may act as a multifunctional activator/repressor that plays separate roles under standard versus stress conditions, but this function has been largely lost in the lab strains. Population analysis suggests that the lab strain, and several wild strains, harbor mutations that diminish Mig3p function. Thus, by expanding our attention to multiple genetic backgrounds, we have uncovered an important missing link in a key metabolic response.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE40153 | GEO | 2012/11/01

SECONDARY ACCESSION(S): PRJNA172935

REPOSITORIES: GEO

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Natural variation in the yeast glucose-signaling network reveals a new role for the Mig3p transcription factor

Project description:The Crabtree effect, in which fermentative metabolism is preferred at the expense of respiration, is a hallmark of budding yeast’s glucose response and a model for the Warburg effect in human tumors. While the glucose-responsive transcriptional repressors Mig1p and Mig2p play well-characterized roles in the Crabtree effect, little function for the related Mig3p transcription factor has been uncovered despite numerous investigations of laboratory yeast strains. Here we studied a wild isolate of Saccharomyces cerevisiae to uncover a critical role for Mig3p that has been lost in S288c-derived laboratory strains. We found that Mig3p affects the expression of hundreds of glucose-responsive genes in the oak strain YPS163, both during growth under standard conditions and upon ethanol treatment. Our results suggest that Mig3p may act as a multifunctional activator/repressor that plays separate roles under standard versus stress conditions, but this function has been largely lost in the lab strains. Population analysis suggests that the lab strain, and several wild strains, harbor mutations that diminish Mig3p function. Thus, by expanding our attention to multiple genetic backgrounds, we have uncovered an important missing link in a key metabolic response. We performed a series of microarray experiments comparing the gene expression response of unstressed or EtOH stressed wild-type or mig3∆ strains in either the BY4741 or YPS163 background (biological triplicates). We also compared gene expression for in reciprocal hemizygous strains (YPS163/BY4741mig3∆ and YPS163mig3∆/BY4742; biological duplicates). Lastly, we measured the gene expression of BY4741 over-expressing BY_MIG3 via galactose induction (biological triplicates).

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Project description:In a previous study, we identified extensive natural variation in the response to acute ethanol treatment in three yeast strains: a lab strain derived from the commonly used S288c (DBY8268), vineyard isolate M22, and oak soil strain YPS163. Many expression differences persisted across several modules of co-regulated genes, implicating trans-acting systemic differences in ethanol sensing and/or response. To understand the genetic basis for these expression differences, we performed eQTL mapping analysis of the response to acute ethanol stress in ~100 F2 strains from two crosses: DBY8268x M22 and DBY8268 x YPS163.

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