3 DIFFERENT REGULATORY MECHANISMS ENABLE YEAST HEXOSE TRANSPORTER (HXT) GENES TO BE INDUCED BY DIFFERENT LEVELS OF GLUCOSE

The HXT genes (HXT1 to HXT4) of the yeast Saccharomyces cerevisiae enc ode hexose transporters, We found that transcription of these genes is induced 10- to 300-fold by glucose. Analysis of glucose induction of HXT gene expression revealed three types of regulation: (i) induction by glucose independent of sugar concentration (HXT3); (ii) induction b y low levels of glucose and repression at high glucose concentrations (HXT2 and HXT4); and (iii) induction only at high glucose concentratio ns (HXT1). The lack of expression of all four HXT genes in the absence of glucose is due to a repression mechanism that requires Rgt1p and S sn6p. GRR1 seems to encode a positive regulator of HXT expression, sin ce grr1 mutants are defective in glucose induction of all four HXT gen es. Mutations in RGT1 suppress the defect in HXT expression caused by grr1 mutations, leading us to propose that glucose induces HXT express ion by activating Grr1p, which inhibits the function of the Rgt1p repr essor. HXT1 expression is also induced by high glucose levels through another regulatory mechanism: rgt1 mutants still require high levels o f glucose for maximal induction of HXT1 expression. The lack of induct ion of HXT2 and HXT4 expression on high levels of glucose is due to gl ucose repression: these genes become induced at high glucose concentra tions in glucose repression mutants (hxk2, reg1, ssn6, tup1, or mig1). Components of the glucose repression pathway (Hxk2p and Reg1p) are al so required for generation of the high-level glucose induction signal for expression of the HXT1 gene. Thus, the glucose repression and gluc ose induction mechanisms share some of the same components and may sha re the same primary signal generated from glucose.