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Promoter Architecture Dictates Variability in Gene Expression

Jones, Daniel L. and Brewster, Robert and Phillips, Rob (2014) Promoter Architecture Dictates Variability in Gene Expression. Biophysical Journal, 106 (2). 489A. ISSN 0006-3495. https://resolver.caltech.edu/CaltechAUTHORS:20140710-080835668

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Abstract

Recent experimental studies have reported that cell-to-cell variability in gene expression is a universal function of mean gene expression levels, implying that knowledge of mean levels of gene expression alone is sufficient to determine the level of variability. This result seems at odds with the physical intuition underlying efforts in the literature to predict the level of variability for different promoter architectures (where we take “promoter architecture” to mean the numbers, positions, and strengths of transcription factor and RNA polymerase binding sites). For instance, we would expect slow TF binding/unbinding kinetics to yield a relatively higher level of variability at a given mean than fast kinetics, as the switching between distinct transcriptional states will yield a broad distribution in mRNA production. To address this apparent conundrum, we constructed a set of 18 constitutive (unregulated) promoters with expression levels spanning a range of 2.5 orders of magnitude, and found that the observed mRNA distributions were consistent with Poissonian production of mRNA. We then placed one of these promoters under regulation by the repressor transcription factor LacI, and measured the resulting mRNA distributions at a range of LacI concentrations. We found that, for the regulated promoter, the level of variability as a function of mean expression followed a distinct, promoter architecture dependent curve as compared with the unregulated promoter. These results demonstrate that the level of variability in gene expression depends on the specific promoter architecture in play.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.bpj.2013.11.4481DOIArticle
http://www.sciencedirect.com/science/article/pii/S0006349513057408PublisherArticle
http://www.biophysics.org/2014meeting/Main/tabid/4177/Default.aspxOrganizationConference Website
ORCID:
AuthorORCID
Jones, Daniel L.0000-0002-7902-996X
Phillips, Rob0000-0003-3082-2809
Additional Information:© 2014 Biophysical Society. Published by Elsevier Inc.
Issue or Number:2
Record Number:CaltechAUTHORS:20140710-080835668
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20140710-080835668
Official Citation:Daniel L. Jones, Robert Brewster, Rob Phillips, Promoter Architecture Dictates Variability in Gene Expression, Biophysical Journal, Volume 106, Issue 2, Supplement 1, 28 January 2014, Page 489a, ISSN 0006-3495, http://dx.doi.org/10.1016/j.bpj.2013.11.4481. (http://www.sciencedirect.com/science/article/pii/S0006349513057408)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:47115
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:10 Jul 2014 15:18
Last Modified:09 Mar 2020 13:19

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