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Steady-state analysis of glucose repression reveals hierarchical expression of proteins under Mig1p control in Saccharomyces cerevisiae.

ABSTRACT: Glucose repression is a global transcriptional regulatory mechanism commonly observed in micro-organisms for the repression of enzymes that are not essential for glucose metabolism. In Saccharomyces cerevisiae, Mig1p, a homologue of Wilms' tumour protein, is a global repressor protein dedicated to glucose repression. Mig1p represses genes either by binding directly to the upstream repression sequence of structural genes or by indirectly repressing a transcriptional activator, such as Gal4p. In addition, some genes are repressed by both of the above mechanisms. This raises a fundamental question regarding the physiological relevance of the varied mechanisms of repression that exist involving Mig1p. We address this issue by comparing two well-known glucose-repression systems, that is, SUC2 and GAL gene expression systems, which encompass all the above three mechanisms. We demonstrate using steady-state analysis that these mechanisms lead to a hierarchical glucose repression profile of different family of genes. This switch over from one carbon source to another is well-calibrated as a function of glucose concentration through this hierarchical transcriptional response. The mechanisms prevailing in this repression system can achieve amplification and sensitivity, as observed in the well-characterized MAPK (mitogen-activated protein kinase) cascade system, albeit through a different structure. A critical feature of repression predicted by our steady-state model for the mutant strain of S. cerevisiae lacking Gal80p agrees well with the data reported here as well as that available in the literature.

SUBMITTER: Verma M

PROVIDER: S-EPMC1183464 | biostudies-literature | 2005 Jun

REPOSITORIES: biostudies-literature

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Steady-state analysis of glucose repression reveals hierarchical expression of proteins under Mig1p control in Saccharomyces cerevisiae.

Verma Malkhey M Bhat Paike J PJ Venkatesh K V KV

The Biochemical journal 20050601 Pt 3

Glucose repression is a global transcriptional regulatory mechanism commonly observed in micro-organisms for the repression of enzymes that are not essential for glucose metabolism. In Saccharomyces cerevisiae, Mig1p, a homologue of Wilms' tumour protein, is a global repressor protein dedicated to glucose repression. Mig1p represses genes either by binding directly to the upstream repression sequence of structural genes or by indirectly repressing a transcriptional activator, such as Gal4p. In a ...[more]

PMID: 15698380

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Project description:Cell growth rate is regulated in response to the abundance and molecular form of essential nutrients. InSaccharomyces cerevisiae(budding yeast), the molecular form of environmental nitrogen is a major determinant of cell growth rate, supporting growth rates that vary at least threefold. Transcriptional control of nitrogen use is mediated in large part by nitrogen catabolite repression (NCR), which results in the repression of specific transcripts in the presence of a preferred nitrogen source that supports a fast growth rate, such as glutamine, that are otherwise expressed in the presence of a nonpreferred nitrogen source, such as proline, which supports a slower growth rate. Differential expression of the NCR regulon and additional nitrogen-responsive genes results in >500 transcripts that are differentially expressed in cells growing in the presence of different nitrogen sources in batch cultures. Here we find that in growth rate-controlled cultures using nitrogen-limited chemostats, gene expression programs are strikingly similar regardless of nitrogen source. NCR expression is derepressed in all nitrogen-limiting chemostat conditions regardless of nitrogen source, and in these conditions, only 34 transcripts exhibit nitrogen source-specific differential gene expression. Addition of either the preferred nitrogen source, glutamine, or the nonpreferred nitrogen source, proline, to cells growing in nitrogen-limited chemostats results in rapid, dose-dependent repression of the NCR regulon. Using a novel means of computational normalization to compare global gene expression programs in steady-state and dynamic conditions, we find evidence that the addition of nitrogen to nitrogen-limited cells results in the transient overproduction of transcripts required for protein translation. Simultaneously, we find that that accelerated mRNA degradation underlies the rapid clearing of a subset of transcripts, which is most pronounced for the highly expressed NCR-regulated permease genesGAP1,MEP2,DAL5,PUT4, andDIP5 Our results reveal novel aspects of nitrogen-regulated gene expression and highlight the need for a quantitative approach to study how the cell coordinates protein translation and nitrogen assimilation to optimize cell growth in different environments.

Dataset Information

Steady-state analysis of glucose repression reveals hierarchical expression of proteins under Mig1p control in Saccharomyces cerevisiae.

Publications

Steady-state analysis of glucose repression reveals hierarchical expression of proteins under Mig1p control in Saccharomyces cerevisiae.

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