TFIIB Autoacetylation in Transcription Initiation

描述(由申请人提供)： 在一般转录因子Lib中发现了一种新的自乙酰化，即乙酰辅酶A中的乙酰基特异性地转移到TFIIB上。这种自催化活性不仅对任何转录因子都是新的，而且TFIIB的乙酰化在体外和细胞内都极大地改变了转录功能。TFIIB和TFIIF之间的相互作用是通过TFIIB的赖氨酸238乙酰化来稳定的。因此，这一体系对于两个层面的研究都很重要。首先，TFIIB乙酰化对转录活性的影响表明，它可能是聚合酶II转录的一种新的调控途径。建议进一步研究TFIIB和TFIIF相互作用的变化，绘制相互作用面，更好地确定乙酰基TFllB对预启动转录复合体的影响。其次，通过对乙酰辅酶A与TFIIB相互作用的结构和化学分析，确定了TFIIB的自乙酰化反应机理。了解这一新的转录调控机制可能最终有助于揭示疾病，并将其应用于基因治疗。

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.