Combinatorial control of gene expression by the three yeast repressors Mig1, Mig2 and Mig3

Westholm, Jakub Orzechowski; Nordberg, Niklas; Murén, Eva; Ameur, Adam; Komorowski, Jan; Ronne, Hans

doi:10.1186/1471-2164-9-601

Cited by 92 publications

(102 citation statements)

References 72 publications

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“…Mig1-binding sites (AATGCGGGGK or SYGGGG) are not found upstream of the filamentation target genes MSB2, KSS1, PGU1, SVS1, YLRO42C, STE12, and TEC1, which might suggest that simply switching these proteins from repressors to activators cannot explain the change in the function of these proteins. DNA microarray data on genes upregulated by Mig1 and Mig2 does not include filamentous growth pathway regulators (Westholm et al 2008). Nevertheless, Mig1 and Mig2 may modulate nutritional scavenging by repression of GAL/ SUC and other genes in the nucleus.…”

Section: Mig1 and Mig2 Proteins Connect Glucose Signaling To Mapk Regmentioning

confidence: 99%

“…Specifically, five isolates of Ste50, five isolates of Mig1, and one isolate of Mtc1 were identified. Mig2 is a homolog of Mig1 (Lutfiyya and Johnston 1996;Lutfiyya et al 1998;Westholm et al 2008). Mig2 was not identified in the screen but associated with the cytosolic domain of Opy2 by two-hybrid analysis ( Figure 3B).…”

Section: Mig1 and Mig2 Proteins Interact With Opy2mentioning

confidence: 99%

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The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in Saccharomyces cerevisiae

Karunanithi

Cullen

2012

Genetics

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In the budding yeast S. cerevisiae, nutrient limitation induces a MAPK pathway that regulates filamentous growth and biofilm/mat formation. How nutrient levels feed into the regulation of the filamentous growth pathway is not entirely clear. We characterized a newly identified MAPK regulatory protein of the filamentous growth pathway, Opy2. A two-hybrid screen with the cytosolic domain of Opy2 uncovered new interacting partners including a transcriptional repressor that functions in the AMPK pathway, Mig1, and its close functional homolog, Mig2. Mig1 and Mig2 coregulated the filamentous growth pathway in response to glucose limitation, as did the AMP kinase Snf1. In addition to associating with Opy2, Mig1 and Mig2 interacted with other regulators of the filamentous growth pathway including the cytosolic domain of the signaling mucin Msb2, the MAP kinase kinase Ste7, and the MAP kinase Kss1. As for Opy2, Mig1 overproduction dampened the pheromone response pathway, which implicates Mig1 and Opy2 as potential regulators of pathway specificity. Taken together, our findings provide the first regulatory link in yeast between components of the AMPK pathway and a MAPK pathway that controls cellular differentiation.

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Section: Mig1 and Mig2 Proteins Connect Glucose Signaling To Mapk Regmentioning

confidence: 99%

Section: Mig1 and Mig2 Proteins Interact With Opy2mentioning

confidence: 99%

The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in Saccharomyces cerevisiae

Karunanithi

Cullen

2012

Genetics

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“…Eds1 is the closest homolog of Rgt1, also a repressor, which regulates glucose transporters. The promoter of EDS1 contains a significant binding site for Mig1/Mig2, major enforcers of glucose repression whose targets also include glucose transporters, and EDS1 is differentially expressed in the mig1, mig2 double mutant but not in either single mutant (Westholm et al 2008). Thus, Eds1 may link lysine biosynthesis to glucose availability and the fermentative/oxidative balance.…”

Section: Identifying Novel Tf Functionsmentioning

confidence: 99%

Mapping functional transcription factor networks from gene expression data

et al. 2013

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A critical step in understanding how a genome functions is determining which transcription factors (TFs) regulate each gene. Accordingly, extensive effort has been devoted to mapping TF networks. In Saccharomyces cerevisiae, protein–DNA interactions have been identified for most TFs by ChIP-chip, and expression profiling has been done on strains deleted for most TFs. These studies revealed that there is little overlap between the genes whose promoters are bound by a TF and those whose expression changes when the TF is deleted, leaving us without a definitive TF network for any eukaryote and without an efficient method for mapping functional TF networks. This paper describes NetProphet, a novel algorithm that improves the efficiency of network mapping from gene expression data. NetProphet exploits a fundamental observation about the nature of TF networks: The response to disrupting or overexpressing a TF is strongest on its direct targets and dissipates rapidly as it propagates through the network. Using S. cerevisiae data, we show that NetProphet can predict thousands of direct, functional regulatory interactions, using only gene expression data. The targets that NetProphet predicts for a TF are at least as likely to have sites matching the TF's binding specificity as the targets implicated by ChIP. Unlike most ChIP targets, the NetProphet targets also show evidence of functional regulation. This suggests a surprising conclusion: The best way to begin mapping direct, functional TF-promoter interactions may not be by measuring binding. We also show that NetProphet yields new insights into the functions of several yeast TFs, including a well-studied TF, Cbf1, and a completely unstudied TF, Eds1.

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“…However, the reduced expression of these genes is likely an indirect effect caused by repression of this set of genes by Mig2, a transcriptional repressor with DNA binding specificity similar to Mig1 (34), but whose expression increases when Rgt1-Mth1/Std1 is inactivated (14). The 15-fold higher levels of Mig2 that result when both MTH1 and STD1 are deleted may be causing reduced expression of this set of 60 genes, 19 of which are known targets of Mig1/Mig2 repression (35).…”

Section: Analysis Of Gene Expression Reveals An Overlap Of Targetsmentioning

confidence: 99%

Asymmetric Signal Transduction through Paralogs That Comprise a Genetic Switch for Sugar Sensing in Saccharomyces cerevisiae

Sabina

Johnston

2009

Journal of Biological Chemistry

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Efficient uptake of glucose is especially critical to Saccharomyces cerevisiae because its preference to ferment this carbon source demands high flux through glycolysis. Glucose induces expression of HXT genes encoding hexose transporters through a signal generated by the Snf3 and Rgt2 glucose sensors that leads to depletion of the transcriptional regulators Mth1 and Std1. These paralogous proteins bind to Rgt1 and enable it to repress expression of HXT genes. Here we show that Mth1 and Std1 can substitute for one another and provide nearly normal regulation of their targets. However, their roles in the glucose signal transduction cascade have diverged significantly. Mth1 is the prominent effector of Rgt1 function because it is the more abundant of the two paralogs under conditions in which both are active (in the absence of glucose). Moreover, the cellular level of Mth1 is quite sensitive to the amount of available glucose. The abundance of Std1 protein, on the other hand, remains essentially constant over a similar range of glucose concentrations. The signal generated by low levels of glucose is amplified by rapid depletion of Mth1; the velocity of this depletion is dependent on both its rate of degradation and swift repression of MTH1 transcription by the Snf1-Mig1 glucose repression pathway. Quantitation of the contributions of Mth1 and Std1 to regulation of HXT expression reveals the unique roles played by each paralog in integrating nutrient availability with metabolic capacity: Mth1 is the primary regulator; Std1 serves to buffer the response to glucose.

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Combinatorial control of gene expression by the three yeast repressors Mig1, Mig2 and Mig3

Cited by 92 publications

References 72 publications

The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in Saccharomyces cerevisiae

The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in Saccharomyces cerevisiae

Mapping functional transcription factor networks from gene expression data

Asymmetric Signal Transduction through Paralogs That Comprise a Genetic Switch for Sugar Sensing in Saccharomyces cerevisiae

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