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 A. Piasecka A1 H. Aldeborgh A1 G. Basishvili A1 W. L. Liu YR 2017 UL http://biorxiv.org/content/early/2017/02/24/083014.abstract AB The p53 tumor suppressor protein is a central regulator that turns on vast gene networks to maintain cellular integrity upon various stimuli. p53 activates transcription initiation in part by aiding recruitment of TFIID to the promoter. 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 demonstrates that TFIID alone binds poorly to native p53 target promoters. p53 unlocks TFIID’s ability to bind DNA by increasing TFIID contacts with both the core promoter and a region surrounding p53’s response element (RE). Analysis of single molecule dissociation kinetics reveals that TFIID interacts with promoters via transient and prolonged DNA binding modes that are each regulated by p53. Importantly, our structural work reveals that TFIID’s conversion from a canonical form to a rearranged DNA-binding conformation is enhanced in the presence of DNA and p53. Notably, TFIID’s interaction with DNA induces p53 to rapidly dissociate, effectively liberating the RE on the promoter. Collectively, these findings indicate that p53 dynamically escorts and loads the basal transcription machinery onto its target promoters.