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An allosteric theory of transcription factor induction

Razo-Mejia, Manuel and Barnes, Stephanie L. and Belliveau, Nathan M. and Chure, Griffin and Einav, Tal and Phillips, Rob (2017) An allosteric theory of transcription factor induction. . (Submitted) http://resolver.caltech.edu/CaltechAUTHORS:20170619-150117855

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Abstract

Allosteric molecules serve as regulators of cellular activity across all domains of life. We present a general theory of allosteric transcriptional regulation that permits quantitative predictions for how physiological responses are tuned to environmental stimuli. To test the model's predictive power, we apply it to the specific case of the ubiquitous simple repression motif in bacteria. We measure the fold-change in gene expression at different inducer concentrations in a collection of strains that span a range of repressor copy numbers and operator binding strengths. After inferring the inducer dissociation constants using data from one of these strains, we show the broad reach of the model by predicting the induction profiles of all other strains. Finally, we derive an expression for the free energy of allosteric transcription factors which enables us to collapse the data from all of our experiments onto a single master curve, capturing the diverse phenomenology of the induction profiles.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1101/111013DOIDiscussion Paper
http://biorxiv.org/content/early/2017/02/22/111013OrganizationDiscussion Paper
ORCID:
AuthorORCID
Razo-Mejia, Manuel0000-0002-9510-0527
Barnes, Stephanie L.0000-0002-5237-603X
Belliveau, Nathan M.0000-0002-1536-1963
Chure, Griffin0000-0002-2216-2057
Einav, Tal0000-0003-0777-1193
Phillips, Rob0000-0003-3082-2809
Additional Information:The copyright holder for this preprint is the author/funder. It is made available under a CC-BY 4.0 International license. This work has been a wonderful exercise in scientific collaboration. We thank Hernan Garcia for information and advice for working with these bacterial strains, Pamela Björkman and Rachel Galimidi for access and training for use of the Miltenyi Biotec MACSQuant flow cytometer, and Colin deBakker of Milteny Biotec for useful advice and instruction in flow cytometry. The experimental front of this work began at the Physiology summer course at the Marine Biological Laboratory in Woods Hole, MA operated by the University of Chicago. We thank Simon Alamos, Nalin Ratnayeke, and Shane McInally for their work on the project during the course. We also thank Suzannah Beeler, Justin Bois, Robert Brewster, Soichi Hirokawa, Jané Kondev, Heun Jin Lee, Mitch Lewis, Muir Morrison, and Julie Theriot for useful advice and discussion. This work was supported by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech, and the National Institutes of Health DP1 OD000217 (Director's Pioneer Award), R01 GM085286, and 1R35 GM118043-01 (MIRA). Nathan Belliveau is a Howard Hughes Medical Institute International Student Research fellow. The authors have declared that no competing interests exist.
Funders:
Funding AgencyGrant Number
La Fondation Pierre-Gilles de GennesUNSPECIFIED
Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
NIHDP1 OD000217
NIHR01 GM085286
NIH1R35 GM118043-01
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Record Number:CaltechAUTHORS:20170619-150117855
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20170619-150117855
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:78340
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:19 Jun 2017 22:26
Last Modified:19 Jun 2017 22:26

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