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How the avidity of polymerase binding to the –35/–10 promoter sites affects gene expression

Einav, Tal and Phillips, Rob (2019) How the avidity of polymerase binding to the –35/–10 promoter sites affects gene expression. Proceedings of the National Academy of Sciences of the United States of America, 116 (27). pp. 13340-13345. ISSN 0027-8424. PMCID PMC6613100. https://resolver.caltech.edu/CaltechAUTHORS:20190405-094702005

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Abstract

Although the key promoter elements necessary to drive transcription in Escherichia coli have long been understood, we still cannot predict the behavior of arbitrary novel promoters, hampering our ability to characterize the myriad sequenced regulatory architectures as well as to design new synthetic circuits. This work builds upon a beautiful recent experiment by Urtecho et al. [G. Urtecho, et al., Biochemistry, 68, 1539–1551 (2019)] who measured the gene expression of over 10,000 promoters spanning all possible combinations of a small set of regulatory elements. Using these data, we demonstrate that a central claim in energy matrix models of gene expression—that each promoter element contributes independently and additively to gene expression—contradicts experimental measurements. We propose that a key missing ingredient from such models is the avidity between the –35 and –10 RNA polymerase binding sites and develop what we call a multivalent model that incorporates this effect and can successfully characterize the full suite of gene expression data. We explore several applications of this framework, namely, how multivalent binding at the –35 and –10 sites can buffer RNA polymerase (RNAP) kinetics against mutations and how promoters that bind overly tightly to RNA polymerase can inhibit gene expression. The success of our approach suggests that avidity represents a key physical principle governing the interaction of RNA polymerase to its promoter.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1073/pnas.1905615116DOIArticle
https://www.pnas.org/content/suppl/2019/06/13/1905615116.DCSupplementalPublisherSupporting Information
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613100/PubMed CentralArticle
https://arxiv.org/abs/1904.01847arXivDiscussion Paper
https://doi.org/10.1101/597989DOIDiscussion Paper
ORCID:
AuthorORCID
Einav, Tal0000-0003-0777-1193
Phillips, Rob0000-0003-3082-2809
Additional Information:© 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). Edited by Ken A. Dill, Stony Brook University, Stony Brook, NY, and approved May 16, 2019 (received for review April 3, 2019). PNAS first published June 13, 2019. We thank Suzy Beeler, Vahe Galstyan, Peng (Brian) He, and Zofii Kaczmarek for helpful discussions. This work was supported by the Rosen Center at the California Institute of Technology and the National Institutes of Health through Grant 1R35 GM118043-01. Author contributions: T.E. designed research; T.E. and R.P. performed research; T.E. analyzed data; and T.E. and R.P. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1905615116/-/DCSupplemental.
Group:Rosen Bioengineering Center
Funders:
Funding AgencyGrant Number
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
NIH1R35 GM118043-01
Subject Keywords:transcription regulation; avidity; statistical mechanics
Issue or Number:27
PubMed Central ID:PMC6613100
Record Number:CaltechAUTHORS:20190405-094702005
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190405-094702005
Official Citation:How the avidity of polymerase binding to the –35/–10 promoter sites affects gene expression. Tal Einav, Rob Phillips. Proceedings of the National Academy of Sciences Jul 2019, 116 (27) 13340-13345; DOI: 10.1073/pnas.1905615116
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94497
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:05 Apr 2019 16:57
Last Modified:18 Dec 2019 17:12

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