RT Journal Article
SR Electronic
T1 p53 dynamically directs TFIID assembly on target gene promoters
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 083014
DO 10.1101/083014
A1 R. A. Coleman
A1 Z. Qiao
A1 S. K Singh
A1 C. S. Peng
A1 M. Cianfrocco
A1 Z. Zhang
A1 L. Song
A1 A. Piasecka
A1 H. Aldeborgh
A1 G. Basishvili
A1 W. Rice
A1 W. L. Liu
YR 2016
UL http://biorxiv.org/content/early/2016/10/24/083014.abstract
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.