THE SACCHAROMYCES-CEREVISIAE CDC68 TRANSCRIPTION ACTIVATOR IS ANTAGONIZED BY SAN1, A PROTEIN IMPLICATED IN TRANSCRIPTIONAL SILENCING

The CDC68 gene (also called SPT16) encodes a transcription factor for the expression of a diverse set of genes in the budding yeast Saccharo myces cerevisiae. To identify other proteins that are functionally rel ated to the Cdc68 protein, we searched for genetic suppressors of a cd c68 mutation. Four suppressor genes in which mutations reverse the tem perature sensitivity imposed by the cdc68-1 mutation were found. We sh ow here that one of the suppressor genes is the previously reported SA N1 gene; san1 mutations were originally identified as suppressors of a sir4 mutation, implicated in the chromatin-mediated transcriptional s ilencing of the two mating-type loci HML and HMR. Each san1 mutation, including a san1 null allele, reversed all aspects of the cdc68 mutant phenotype. Conversely, increased copy number of the wild-type SAN1 ge ne lowered the restrictive temperature for the cdc68-1 mutation. Our f indings suggest that the San1 protein antagonizes the transcriptional activator function of the Cdc68 protein. The identification of san1 mu tations as suppressors of cdc68 mutations suggests a role for Cdc68 in chromatin structure.