Very low amounts of glucose cause repression of the stress-responsive geneHSP12 in Saccharomyces cerevisiae

Changing the growth mode of Saccharomyces cerevisiae by adding fermentable amounts of glucose to cells growing on a non-fermentable carbon source lead s to rapid repression of general stress-responsive genes like HSP12, Remark ably, glucose repression of HSP12 appeared to occur even at very low glucos e concentrations, down to 0.005%. Although these low levels of glucose do n ot induce fermentative growth, they do act as a growth signal, since upon a ddition of glucose to a concentration of 0.02%, growth rate increased and r ibosomal protein gene transcription was up-regulated, In an attempt to eluc idate how this type of glucose signalling may operate, several signalling m utants were examined, Consistent with the low amounts of glucose that elici t HSP12 repression, neither the main glucose-repression pathway nor cAMP-de pendent activation of protein kinase A appeared to play a role in this regu lation, Using mutants involved in glucose metabolism, evidence was obtained suggesting that glucose 6-phosphate serves as a signalling molecule, To id entify the target for glucose repression on the promoter of the HSP12 gene, a promoter deletion series was used. The major transcription factors gover ning (stress-induced) transcriptional activation of HSP12 are Msn2p and Msn 4p, binding to the general stress-responsive promoter elements (STREs). Sur prisingly, glucose repression of HSP12 appeared to be independent of Msn2/4 p: HSP12 transcription in glycerol-grown cells was unaffected in a Delta ms n2 Delta msn4 strain, Nevertheless, evidence was obtained that STRE-mediate d transcription is the target of repression by low amounts of glucose. Thes e data suggest that an as yet unidentified factor is involved in STRE-media ted transcriptional regulation of HSP12.