The conformation of the transcription factor TFIIB modulates the response to transcriptional activators in vivo

The general transcription factor TFIIB plays a crucial role in the assembly of the transcriptional preinitiation complex and has also been proposed as a target of transcriptional activator proteins (reviewed in [1]). TFIIB is composed of two domains which are engaged in an intramolecular interaction that is disrupted upon interaction with the activation domain of the Herpe svirus VP16 protein in vitro [2,3], The significance of this event for tran scriptional activation is not known, however. The amino-terminal intramolec ular interaction domain is the most conserved region of TFIIB and plays a r ole in transcription start-site selection [4-6]. in addition, we have shown previously that the integrity of this region is required for transcription al activation in vivo [4], Here, we have defined a charge cluster at the am ino terminus of TFIIB that is required for transcriptional activation in vi vo. We found that this domain determines the affinity of the TFIIB intramol ecular interaction and the ability of TFIIB to interact with a transcriptio nal activation domain, but not with components of the holoenzyme, Our resul ts suggest that the intramolecular interaction in TFIIB regulates transcrip tional activation in vivo.