PT  - JOURNAL ARTICLE
AU  - R. A. Coleman
AU  - Z. Qiao
AU  - S. K Singh
AU  - C. S. Peng
AU  - M. Cianfrocco
AU  - Z. Zhang
AU  - L. Song
AU  - A. Piasecka
AU  - H. Aldeborgh
AU  - G. Basishvili
AU  - W. Rice
AU  - W. L. Liu
TI  - p53 dynamically directs TFIID assembly on target gene promoters
AID  - 10.1101/083014
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 083014
4099  - http://biorxiv.org/content/early/2016/10/24/083014.short
4100  - http://biorxiv.org/content/early/2016/10/24/083014.full
AB  - p53 is a central regulator in tumor suppression. In response to various signals, p53 turns on vast gene networks to maintain cellular integrity, in part by aiding promoter recruitment of the TFIID-mediated transcription machinery to stimulate transcription initiation. However, the precise means by which p53 dynamically interacts with TFIID to facilitate assembly on target gene promoters remains elusive. To address this key question, we have undertaken an integrated approach involving single molecule fluorescence microscopy, single particle cryo-electron microscopy, and biochemistry. Our real-time single molecule imaging demonstrated that p53 both delivers and promotes the stable binding of TFIID to DNA. Furthermore, TFIID binds core promoter sequences via distinct modes displaying transient and prolonged stability. Importantly, TFIID’s interaction with DNA induces p53 to rapidly dissociate, effectively recycling p53’s binding site on the promoter. This notion is further supported by our structural studies. In addition, upstream promoter DNA comprising p53’s response elements is highly mobile when bound to TFIID compared to the core promoter DNA. Collectively, these findings indicate that p53 serves as an escort to dynamically recruit and load the basal transcription machinery onto its target promoters by regulating the structural architecture of TFIID.