Abstract
BackgroundThe SNF3 gene in the yeast Saccharomyces cerevisiae encodes a low glucose sensor that regulates expression of an important subset of the hexose transporter (HXT) superfamily. Null mutations of snf3 result in a defect in growth on low glucose concentrations due to the inability to relieve repression of a subset of the HXT genes. The snf3 null mutation phenotype is suppressed by the loss of either one of the downstream co-repressor proteins Rgt1p or Mth1p. The relief of repression allows expression of HXT transporter proteins, the resumption of glucose uptake and therefore of growth in the absence of a functional Snf3 sensor.ResultsStrains heterozygous for both the RGT1 and MTH1 genes (RGT1/rgt1Δ MTH1/mth1Δ snf3Δ/snf3Δ) but homozygous for the snf3∆ were found to grow on low glucose. Since null alleles in the heterozygous state lead to suppression, MTH1 and RGT1 display the phenomenon of combined haploinsufficiency. This observed haploinsufficiency is consistent with the finding of repressor titration as a mechanism of suppression of snf3. Mutants of the STD1 homolog of MTH1 did not display haploinsufficiency singly or in combination with mutations in RGT1. HXT gene reporter fusion assays indicated that the presence of heterozygosity at the MTH1 and RGT1 alleles leads to increased expression of the HXT2 gene. Deletion of the HXT2 gene in a heterozygous diploid, RGT1/rgt1Δ MTH1/mth1Δ snf3Δ/snf3Δ hxt2Δ/hxt2Δ, prevented the suppression of snf3Δ.ConclusionsThese findings support the model of relief of repression as the mechanism of restoration of growth on low glucose concentrations in the absence of functional Snf3p. Further, the observation that HXT2 is the gene responsible for restoration of growth under these conditions suggests that the numbers of repressor binding domains found in the regulatory regions of members of the HXT family may have biological relevance and enable differential regulation.
Highlights
The SNF3 gene in the yeast Saccharomyces cerevisiae encodes a low glucose sensor that regulates expression of an important subset of the hexose transporter (HXT) superfamily
MTH1 and RGT1 display combined haploinsufficiency The MTH1 gene encodes a co-repressor protein that is able to bind to the repressor RGT1 stabilizing binding of the complex to the regulatory regions of the HXT genes
In the course of analysis of missense mutations in rgt1 and mth1 we observed suppression of the snf3Δ growth defect on low glucose in strains that were heterozygous at these loci
Summary
The SNF3 gene in the yeast Saccharomyces cerevisiae encodes a low glucose sensor that regulates expression of an important subset of the hexose transporter (HXT) superfamily. Null mutations of snf result in a defect in growth on low glucose concentrations due to the inability to relieve repression of a subset of the HXT genes. Many signaling pathways are known to converge at the promoters of the HXT genes to either positively or negatively regulate specific transporters in response to their respective inputs These pathways include: glucose induction, glucose repression, High Osmolarity Glycerol (HOG), Target of Rapamycin (TOR) GCR1/GCR2 pathway and the RAS/PKA pathway [3,4,5,6,7,8]. Null alleles of snf result in the loss of fermentative growth on low levels of glucose (0.05%) while null alleles of both sensors result in the loss of fermentative growth on 2% glucose [11,15,16]
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