Combinatorial control of gene expression by the three yeast repressors Mig 1 , Mig 2 and Mig 3 Jakub

Background: Expression of a large number of yeast genes is repressed by glucose. The zinc finger protein Mig1 is the main effector in glucose repression, but yeast also has two related proteins: Mig2 and Mig3. We have used microarrays to study global gene expression in all possible combinations of mig1, mig2 and mig3 deletion mutants. Results: Mig1 and Mig2 repress a largely overlapping set of genes on 2% glucose. Genes that are upregulated in a mig1 mig2 double mutant were grouped according to the contribution of Mig2. Most of them show partially redundant repression, with Mig1 being the major repressor, but some genes show complete redundancy, and some are repressed only by Mig1. Several redundantly repressed genes are involved in phosphate metabolism. The promoters of these genes are enriched for Pho4 sites, a novel GGGAGG motif, and a variant Mig1 site which is absent from genes repressed only by Mig1. Genes repressed only by Mig1 on 2% glucose include the hexose transporter gene HXT4, but Mig2 contributes to HXT4 repression on 10% glucose. HXT6 is one of the few genes that are more strongly repressed by Mig2. Mig3 does not seem to overlap in function with Mig1 and Mig2. Instead, Mig3 downregulates the SIR2 gene encoding a histone deacetylase involved in gene silencing and the control of aging. Conclusion: Mig2 fine-tunes glucose repression by targeting a subset of the Mig1-repressed genes, and by responding to higher glucose concentrations. Mig3 does not target the same genes as Mig1 and Mig2, but instead downregulates the SIR2 gene. Background Gene regulatory networks control gene expression in response to both internal conditions (e.g. cell type, age) and external signals (e.g. nutrients, stress, signaling molecules). The use of combinations of transcription factors in regulatory networks greatly enhances the number of possible gene expression patterns, and enables cells to finetune their response to different conditions. Combinatorial aspects of gene regulation have been studied both on a whole-network scale [1-6] and for specific parts of reguPublished: 16 December 2008 BMC Genomics 2008, 9:601 doi:10.1186/1471-2164-9-601 Received: 6 August 2008 Accepted: 16 December 2008 This article is available from: http://www.biomedcentral.com/1471-2164/9/601 © 2008 Westholm et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.