A new regulatory domain on the TATA-binding protein

Recognition of the TATA box by the TATA-binding protein (TBP) is a highly r egulated step in RNA polymerase II-dependent transcription. Several protein s have been proposed to regulate TBP activity, yet the TBP domains responsi ve to all these regulators have not been defined. Here we describe a new cl ass of TBP mutants that increase transcription from core promoters in vivo. The majority of these mutations alter amino acids that cluster tightly on the TBP surface, defining a new TBP regulatory domain. The mutant TBP prote ins are defective for binding the transcriptional regulator yNC2, are resis tant to inhibition by yNC2 in vitro and exhibit allele-specific genetic int eractions with yNC2. These results provide strong biochemical and genetic e vidence that TBP is directly repressed ill vivo, and define a new TBP domai n important for transcriptional regulation.