A new negative control gene for amino acid biosynthesis in Saccharomyces cerevisiae

Enzyme levels in multiple amino acid biosynthetic pathways in yeast are coregulated. This control is effected largely at the transcriptional level by a number of regulatory genes. We report the isolation and characterization of a new negative regulatory gene, GCD4, for this general control system. GCD4 mutations are recessive and define a single Medelian gene on chromosome III. A gcd4 mutation results in resistance to different amino acid analogs and elevated, but fully inducible, mRNA levels of genes under general control. Epistasis analysis indicates that GCD4 acts more directly than the positive regulators GCN1, GCN2, GCN3 and GCN5, but less directly than GCN4, on the transcription of the amino acid biosynthetic genes. These data imply that GCD4 is a negative regulator of the positive effector, GCN4. Although GCD4 occupies the same position relative to the GCN genes as other GCD genes, it produces a unique phenotype. These results illustrate the diversity of function of negative regulators in general control.