LARGE PROTEIN COMPLEX CONTAINING THE YEAST SIN3P AND RPD3P TRANSCRIPTIONAL REGULATORS

The SIN3 gene is required for the transcriptional repression of divers e genes in Saccharomyces cerevisiae. Sin3p does not bind directly to D NA but is thought to be targeted to promoters by interacting with sequ ence-specific DNA-binding proteins, We show here that Sin3p is present in a large multiprotein complex with an apparent molecular mass, esti mated by gel filtration chromatography, of greater than 2 million Da. Genetic studies have shown that the yeast RPD3 gene has a function sim ilar to that of SIN3 in transcriptional regulation, as SIN3 and RPD3 n egatively regulate the same set of genes. The SIN3 and RPD3 genes are conserved from yeasts to mammals, and recent work suggests that RPD3 m ay encode a histone deacetylase. We show that Rpd3p is present in the Sin3p complex and that an rpd3 mutation eliminates SIN3-dependent repr ession. Thus, Sin3p may function as a bridge to recruit the Rpd3p hist one deacetylase to specific promoters.