TFIIB Autoacetylation in Transcription Initiation

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DESCRIPTION (provided by applicant): A novel autoacetylation in the general transcription factor lIB has been discovered, a specific transfer of the acetyl group in acetyl coenzyme A to TFIIB. Not only is this autocatalytic activity novel for any transcription factor is the acetylation of TFIIB drastically alters transcriptional function both in vitro and in cells. The interaction between TFIIB and TFIIF is stabilized by the acetylation of lysine 238 of TFIIB. This system, then, is important for study on two levels. First, the impact of acetylation of TFIIB on transcriptional activity suggests that it may act as a new regulatory pathway for polymerase II transcription. It is proposed to study further the changed interaction of TFIIB and TFIIF, to map out the interaction surface and better define the effects of acetyl-TFllB on the preinitiation transcriptional complex. Secondly, it is proposed to define a mechanism for the autoacetylation of TFIIB using structural and chemical analysis of the interaction between acetyI-CoA and TFIIB. Understanding this novel regulation of transcription may eventually shed light on disease and have applications in gene therapy.