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Reconciling Kinetic and Equilibrium Models of Bacterial Transcription

Morrison, Muir and Razo-Mejia, Manuel and Phillips, Rob (2020) Reconciling Kinetic and Equilibrium Models of Bacterial Transcription. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20200615-130249775

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Abstract

The study of transcription remains one of the centerpieces of modern biology with implications in settings from development to metabolism to evolution to disease. Precision measurements using a host of different techniques including fluorescence and sequencing readouts have raised the bar for what it means to quantitatively understand transcriptional regulation. In particular our understanding of the simplest genetic circuit is sufficiently refined both experimentally and theoretically that it has become possible to carefully discriminate between different conceptual pictures of how this regulatory system works. This regulatory motif, originally posited by Jacob and Monod in the 1960s, consists of a single transcriptional repressor binding to a promoter site and inhibiting transcription. In this paper, we show how seven distinct models of this so-called simple-repression motif, based both on equilibrium and kinetic thinking, can be used to derive the predicted levels of gene expression and shed light on the often surprising past success of the equilibrium models. These different models are then invoked to confront a variety of different data on mean, variance and full gene expression distributions, illustrating the extent to which such models can and cannot be distinguished, and suggesting a two-state model with a distribution of burst sizes as the most potent of the seven for describing the simple-repression motif.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.06.13.150292DOIDiscussion Paper
https://github.com/RPGroup-PBoC/bursty_transcriptionRelated ItemCode
ORCID:
AuthorORCID
Morrison, Muir0000-0002-0768-7234
Razo-Mejia, Manuel0000-0002-9510-0527
Phillips, Rob0000-0003-3082-2809
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. This version posted June 14, 2020. We thank Rob Brewster for providing the raw single-molecule mRNA FISH data. We thank Justin Bois for his key support with the Bayesian inference section. We would also like to thank Griffin Chure for invaluable feedback on the manuscript. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1745301. This work was also supported by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech, and the NIH 1R35 GM118043 (MIRA). M.R.M. was supported by the Caldwell CEMI fellowship.
Group:Caltech Center for Environmental Microbial Interactions (CEMI), Rosen Bioengineering Center
Funders:
Funding AgencyGrant Number
NSF Graduate Research FellowshipDGE-1745301
La Fondation Pierre-Gilles de GennesUNSPECIFIED
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
NIH1R35 GM118043
Caltech Center for Environmental Microbial Interactions (CEMI)UNSPECIFIED
Record Number:CaltechAUTHORS:20200615-130249775
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200615-130249775
Official Citation:Reconciling Kinetic and Equilibrium Models of Bacterial Transcription. Muir J. Morrison, Manuel Razo-Mejia, Rob Phillips. bioRxiv 2020.06.13.150292; doi: https://doi.org/10.1101/2020.06.13.150292
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103922
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:15 Jun 2020 21:00
Last Modified:15 Jun 2020 21:00

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