Determination of the targets of low glucose signaling in Saccharomyces cerevisiae by the SNF3 glucose sensor

The yeast Saccharomyces cerevisiae dominates a fermentation by exquisitely modulating the uptake of glucose by tightly regulating the expression of specific members of a large family of hexose transporters to precisely match the extracellular concentration and its ability to metabolize this very reactive sugar. Global transcriptional responses are a result of activation of a complex signal transduction pathway that integrates many cellular signaling pathways to maximize fitness. The first step initiating this pathway is the activation by glucose of the low glucose sensor, Snf3p, lying in the outer membrane and passing a signal on to unknown secondary messengers to transcriptionally regulate gene expression. Developing genomic technologies have become available with the completion of the yeast genome sequence to globally assess transcriptional response. Microarray analysis was used to identify potential gene targets of Snf3p mediated transcriptional regulation. Several genes were identified which demonstrated a requirement for the Snf3p low glucose sensor. An intriguing picture emerged from the functional clustering of the genes biased in the wild type strain transcriptome, suggesting a distributed network rather than a simple linear signal transduction pathway. Northern blot analysis on several genes reconfirmed individual microarray results. Expression analysis of HXT2 encoding an important hexose transporter demonstrated that Snf3p is required for sustained expression, but also indicated an additional regulatory component. Attempts to determine the transcriptional state of the highly homologous hexose transporter gene family were mostly unsuccessful due to the technology currently available. The identification of the structure of the mRNA especially the untranslated regions, which shows the highest level of diversity allowing for the development of more specific probes. Globally, yeast strains unable to detect the extracellular glucose respond by derepressing many genes required for the use of alternative carbons sources via the Mig1p and Msn2/4p pathways. Wild type cells maintain this repression and maybe the mechanism of Snf3p glucose sensing.