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 μ promoter (μ) 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 μ promoter. Similarly, TFIIA reverses the repression of transcription by the 90-kDa factor on the MLP but not on the μ promoter. Thus, the interactions of TATA- binding protein, TFIIA, and the 90-kDa factor are promoter-specific.