Srb7p is a physical and physiological target of Tup1p.

The holoenzyme of transcription integrates the positive and negative signals from the promoters of eukaryotic genes. We demonstrate that the essential holoenzyme component Srb7p is a physiologically relevant target of the global repressor Tup1p in Saccharomyces cerevisiae. Tup1p binds Srb7p in vivo and in vitro, and all genes tested that are repressed by Tup1p are derepressed when wild-type Srb7p is replaced by a mutant derivative of Srb7p that is no longer capable of interacting with Tup1p. Therefore, Srb7p is the first holoenzyme component essential for repression by Tup1p for which a physical interaction with Tup1p has been demonstrated. Furthermore, we find that Srb7p also binds Med6p and that this interaction is necessary for full transcriptional activation by different activators. Our finding that Med6p and Tup1p compete for the interaction with Srb7p suggests a model for Tup1p-mediated repression.