A negative cofactor containing Dr1/p19 modulates transcription with TFIIA in a promoter-specific fashion

An activity that modulated the relative levels of transcription from the adenovirus major late promoter (MLP), and the immunoglobulin heavy chain mu promoter (mu) was purified as a 90-kDa factor, This factor is suggested to be a heterotetramer of two subunits: a 20-kDa polypeptide identical to the previously described Dr1/p19 and a novel 30-kDa polypeptide. The Dr1/p19 protein has been characterized as a repressor of transcription, and the 30-kDa protein is related to a recently identified yeast gene proposed to encode a repressor of transcription, The 90-kDa factor forms a complex with TATA-binding protein on DNA and at high concentrations of both factors protects over a 150-base pair region around the promoter from DNase I cleavage, The conformation of this complex as assayed by footprinting analysis is altered by the transcription factor TFIIA on the MLP but not on the mu promoter. Similarly, TFIIA reverses the repression of transcription by the 90-kDa factor on the MLP but not on the mu promoter, Thus, the interactions of TATA-binding protein, TFIIA, and the 90-kDa factor are promoter-specific.