Genetic evidence for similar negative regulatory domains in the yeast transcription activators GAL4 and LAC9.

The GAL4 protein of Saccharomyces cerevisiae and the LAC9 protein of Kluyveromyces lactis are transcription activator proteins with similar structure and function. Greatest similarity occurs in the C region near the carboxy terminus, where 16 of 18 amino acids are identical. The function of the C region is unclear. Here we show that the structural similarity is reflected in functional similarity. Single amino acid changes in the C region of GAL4 and LAC9 create a similar phenotype: constitutive gene expression. In S. cerevisiae the constitutive phenotype caused by GAL4 mutants can be abolished by overproduction of GAL80. These results support a model in which the C region of GAL4 and LAC9 constitute similar negative regulatory domains that interact with GAL80 in S. cerevisiae and an unidentified GAL80 homolog in K. lactis. This protein-protein interaction prevents expression of the galactose operon in the uninduced state.