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

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Science  19 Dec 2014:
Vol. 346, Issue 6216, pp. 1533-1536
DOI: 10.1126/science.1255301

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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.

Promoters tune gene expression noise

Although cells in a tissue are genetically identical and appear the same, they often exhibit variability in their patterns of gene expression. Organisms may need this to prepare for exposure to varying environmental stresses. Using the tools of synthetic biology, Jones et al. construct a wide range of E. coli promoters in which the key molecular parameters (such as protein binding and unbinding rates) are systematically varied and compare the resulting expression noise to parameter -free model predictions. This work demonstrates that expression noise is a tunable parameter, with different generegulatory architectures giving rise to different, but predictable, patterns of expression noise.

Science, this issue p. 1533

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