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Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression

Sanchez, Alvaro and Garcia, Hernan G. and Jones, Daniel and Phillips, Rob and Kondev, Jané (2011) Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression. PLoS Computational Biology, 7 (3). Art. No. e1001100. ISSN 1553-734X. https://resolver.caltech.edu/CaltechAUTHORS:20110422-111812818

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Abstract

According to recent experimental evidence, promoter architecture, defined by the number, strength and regulatory role of the operators that control transcription, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect variability in gene expression in a systematic rather than case-by-case fashion. In this article we make such a systematic investigation, based on a microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcriptional output from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can be used to test kinetic models of gene regulation. The emphasis of the discussion is on prokaryotic gene regulation, but our analysis can be extended to eukaryotic cells as well.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.pcbi.1001100DOIArticle
http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1001100PublisherArticle
Additional Information:© 2011 Sanchez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received August 11, 2010; Accepted January 28, 2011; Published March 3, 2011. Editor: Wyeth W. Wasserman, University of British Columbia, Canada. Funding: RP, HGG and DJ were supported by NIH grants R01 GM085286-01S and R01 GM085286, and National Institutes of Health Director’s Pioneer Award grant DP1 OD000217. JK acknowledges support from National Science Foundation grant DMR-0706458. AS was supported by grants GM81648 and GM43369 from the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We wish to thank Tom Kuhlman, Ido Golding, Terry Hwa, Bob Schleif, Paul Wiggins, Felix Hol, Narendra Mahreshri, T.L. To, C.J. Zopf and Jeff Gelles for many helpful discussions. AS wishes to thank Jeff Gelles and all members of the Gelles lab for their continuous support, as well as Melisa Osborne for her help in editing the manuscript. Author Contributions: Conceived and designed the experiments: AS HGG RP JK. Performed the experiments: AS HGG DJ. Analyzed the data: AS HGG DJ. Contributed reagents/materials/analysis tools: AS HGG DJ. Wrote the paper: AS HGG DJ RP JK.
Funders:
Funding AgencyGrant Number
NIHR01 GM085286-01S
NIHR01 GM085286
NIHDP1 OD000217
NIHGM81648
NIHGM43369
NSFDMR-0706458
Issue or Number:3
Record Number:CaltechAUTHORS:20110422-111812818
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110422-111812818
Official Citation:Sanchez A, Garcia HG, Jones D, Phillips R, Kondev J (2011) Effect of Promoter Architecture on the Cell-to-Cell Variability in Gene Expression. PLoS Comput Biol 7(3): e1001100. doi:10.1371/journal.pcbi.1001100
Usage Policy:This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ID Code:23424
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:17 May 2011 22:28
Last Modified:03 Oct 2019 02:46

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