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Promoter architecture dictates cell-to-cell variability in gene expression

Jones, Daniel L. and Brewster, Robert C. and Phillips, Rob (2014) Promoter architecture dictates cell-to-cell variability in gene expression. Science, 346 (6216). pp. 1533-1536. ISSN 0036-8075. PMCID PMC4388425. https://resolver.caltech.edu/CaltechAUTHORS:20141223-110116617

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Abstract

Variability in gene expression among genetically identical cells has emerged as a central preoccupation in the study of gene regulation; however, a divide exists between the predictions of molecular models of prokaryotic transcriptional regulation and genome-wide experimental studies suggesting that this variability is indifferent to the underlying regulatory architecture. We constructed a set of promoters in Escherichia coli in which promoter strength, transcription factor binding strength, and transcription factor copy numbers are systematically varied, and used messenger RNA (mRNA) fluorescence in situ hybridization to observe how these changes affected variability in gene expression. Our parameter-free models predicted the observed variability; hence, the molecular details of transcription dictate variability in mRNA expression, and transcriptional noise is specifically tunable and thus represents an evolutionarily accessible phenotypic parameter.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.1255301DOIArticle
http://www.sciencemag.org/content/346/6216/1533PublisherArticle
http://www.sciencemag.org/content/346/6216/1533/suppl/DC1PublisherSupplementary Materials
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388425/PubMed CentralArticle
ORCID:
AuthorORCID
Jones, Daniel L.0000-0002-7902-996X
Phillips, Rob0000-0003-3082-2809
Additional Information:© 2014 American Association for the Advancement of Science. Received 28 April 2014; accepted 4 November 2014. We thank H. J. Lee, C. Wiggins, Y. Lin, X. Zhu, F. Weinert, M. Rydenfelt, R. Milo, H. Garcia, N. Belliveau, and J. Sheung for useful discussions. Supported by NIH grants DP1 OD000217 (Directors Pioneer Award), R01 GM085286, and 1 U54 CA143869 (Northwestern PSOC Center); La Fondation Pierre Gilles de Gennes (R.P.); and the Donna and Benjamin M. Rosen Center for Bioengineering at Caltech (D.L.J.). Raw microscopy image data are archived in the Phillips laboratory at Caltech and are available upon request.
Funders:
Funding AgencyGrant Number
NIH Directors Pioneer AwardDP1 OD000217A
NIHR01 GM085286
NIH1 U54 CA143869
La Fondation Pierre Gilles de GennesUNSPECIFIED
Donna and Benjamin M. Rosen Center for BioengineeringUNSPECIFIED
Issue or Number:6216
PubMed Central ID:PMC4388425
Record Number:CaltechAUTHORS:20141223-110116617
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141223-110116617
Official Citation:Promoter architecture dictates cell-to-cell variability in gene expression Daniel L. Jones, Robert C. Brewster, and Rob Phillips Science 19 December 2014: 346 (6216), 1533-1536. [DOI:10.1126/science.1255301]
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:53149
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:23 Dec 2014 19:10
Last Modified:09 Mar 2020 13:19

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