Effect of promoter architecture on the cell-to-cell variability in gene expression.

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 cor...

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Main Authors: Alvaro Sanchez, Hernan G Garcia, Daniel Jones, Rob Phillips, Jané Kondev
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-03-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001100&type=printable
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author Alvaro Sanchez
Hernan G Garcia
Daniel Jones
Rob Phillips
Jané Kondev
author_facet Alvaro Sanchez
Hernan G Garcia
Daniel Jones
Rob Phillips
Jané Kondev
author_sort Alvaro Sanchez
collection DOAJ
description 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.
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spelling doaj-art-468e561343d64f1b9e7e7cd59c35337a2025-08-20T02:34:09ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-03-0173e100110010.1371/journal.pcbi.1001100Effect of promoter architecture on the cell-to-cell variability in gene expression.Alvaro SanchezHernan G GarciaDaniel JonesRob PhillipsJané KondevAccording 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.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001100&type=printable
spellingShingle Alvaro Sanchez
Hernan G Garcia
Daniel Jones
Rob Phillips
Jané Kondev
Effect of promoter architecture on the cell-to-cell variability in gene expression.
PLoS Computational Biology
title Effect of promoter architecture on the cell-to-cell variability in gene expression.
title_full Effect of promoter architecture on the cell-to-cell variability in gene expression.
title_fullStr Effect of promoter architecture on the cell-to-cell variability in gene expression.
title_full_unstemmed Effect of promoter architecture on the cell-to-cell variability in gene expression.
title_short Effect of promoter architecture on the cell-to-cell variability in gene expression.
title_sort effect of promoter architecture on the cell to cell variability in gene expression
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1001100&type=printable
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