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Mol Cell Biol. 2017 Jun 15;37(13). pii: e00085-17. doi: 10.1128/MCB.00085-17. Print 2017 Jul 1.

p53 Dynamically Directs TFIID Assembly on Target Gene Promoters.

Author information

1
Gruss Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA robert.coleman2@einstein.yu.edu.
2
Gruss Lipper Biophotonics Center, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
3
Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA.
4
Surrozen, South San Francisco, California, USA.

Abstract

p53 is a central regulator that turns on vast gene networks to maintain cellular integrity in the presence of 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 issue, we have undertaken an integrated approach involving single-molecule fluorescence microscopy, single-particle cryo-electron microscopy, and biochemistry. Our real-time single-molecule imaging data demonstrate that TFIID alone binds poorly to native p53 target promoters. p53 unlocks TFIID's ability to bind DNA by stabilizing TFIID contacts with both the core promoter and a region within p53's response element. 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 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, which likely leads to additional rounds of p53-mediated recruitment of other basal factors. Collectively, these findings indicate that p53 dynamically escorts and loads TFIID onto its target promoters.

KEYWORDS:

TFIID; p53; single-molecule microscopy; structure; transcription

PMID:
28416636
PMCID:
PMC5472829
DOI:
10.1128/MCB.00085-17
[Indexed for MEDLINE]
Free PMC Article

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