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

Daniel L Jones, Robert C Brewster, Rob Phillips
Author Information
  1. Daniel L Jones: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA.
  2. Robert C Brewster: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
  3. Rob Phillips: Department of Applied Physics, California Institute of Technology, Pasadena, CA 91125, USA. Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. phillips@pboc.caltech.edu.

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.

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Grants

  1. DP1 OD000217/NIH HHS
  2. R01 GM085286/NIGMS NIH HHS
  3. U54 CA143869/NCI NIH HHS
  4. 1 U54 CA143869/NCI NIH HHS

MeSH Term

Cells
DNA-Directed RNA Polymerases
Escherichia coli
Gene Dosage
Gene Expression Regulation
Genetic Variation
In Situ Hybridization
Kinetics
Lac Repressors
Models, Genetic
Promoter Regions, Genetic
Protein Binding
RNA, Messenger
Transcription, Genetic

Chemicals

Lac Repressors
RNA, Messenger
DNA-Directed RNA Polymerases

Word Cloud

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