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A Model for Sigma Factor Competition in Bacterial Cells

Sigma factors control global switches of the genetic expression program in bacteria. Different sigma factors compete for binding to a limited pool of RNA polymerase (RNAP) core enzymes, providing a mechanism for cross-talk between genes or gene classes via the sharing of expression machinery. To ana...

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Autores principales: Mauri, Marco, Klumpp, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191881/
https://www.ncbi.nlm.nih.gov/pubmed/25299042
http://dx.doi.org/10.1371/journal.pcbi.1003845
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author Mauri, Marco
Klumpp, Stefan
author_facet Mauri, Marco
Klumpp, Stefan
author_sort Mauri, Marco
collection PubMed
description Sigma factors control global switches of the genetic expression program in bacteria. Different sigma factors compete for binding to a limited pool of RNA polymerase (RNAP) core enzymes, providing a mechanism for cross-talk between genes or gene classes via the sharing of expression machinery. To analyze the contribution of sigma factor competition to global changes in gene expression, we develop a theoretical model that describes binding between sigma factors and core RNAP, transcription, non-specific binding to DNA and the modulation of the availability of the molecular components. The model is validated by comparison with in vitro competition experiments, with which excellent agreement is found. Transcription is affected via the modulation of the concentrations of the different types of holoenzymes, so saturated promoters are only weakly affected by sigma factor competition. However, in case of overlapping promoters or promoters recognized by two types of sigma factors, we find that even saturated promoters are strongly affected. Active transcription effectively lowers the affinity between the sigma factor driving it and the core RNAP, resulting in complex cross-talk effects. Sigma factor competition is not strongly affected by non-specific binding of core RNAPs, sigma factors and holoenzymes to DNA. Finally, we analyze the role of increased core RNAP availability upon the shut-down of ribosomal RNA transcription during the stringent response. We find that passive up-regulation of alternative sigma-dependent transcription is not only possible, but also displays hypersensitivity based on the sigma factor competition. Our theoretical analysis thus provides support for a significant role of passive control during that global switch of the gene expression program.
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spelling pubmed-41918812014-10-14 A Model for Sigma Factor Competition in Bacterial Cells Mauri, Marco Klumpp, Stefan PLoS Comput Biol Research Article Sigma factors control global switches of the genetic expression program in bacteria. Different sigma factors compete for binding to a limited pool of RNA polymerase (RNAP) core enzymes, providing a mechanism for cross-talk between genes or gene classes via the sharing of expression machinery. To analyze the contribution of sigma factor competition to global changes in gene expression, we develop a theoretical model that describes binding between sigma factors and core RNAP, transcription, non-specific binding to DNA and the modulation of the availability of the molecular components. The model is validated by comparison with in vitro competition experiments, with which excellent agreement is found. Transcription is affected via the modulation of the concentrations of the different types of holoenzymes, so saturated promoters are only weakly affected by sigma factor competition. However, in case of overlapping promoters or promoters recognized by two types of sigma factors, we find that even saturated promoters are strongly affected. Active transcription effectively lowers the affinity between the sigma factor driving it and the core RNAP, resulting in complex cross-talk effects. Sigma factor competition is not strongly affected by non-specific binding of core RNAPs, sigma factors and holoenzymes to DNA. Finally, we analyze the role of increased core RNAP availability upon the shut-down of ribosomal RNA transcription during the stringent response. We find that passive up-regulation of alternative sigma-dependent transcription is not only possible, but also displays hypersensitivity based on the sigma factor competition. Our theoretical analysis thus provides support for a significant role of passive control during that global switch of the gene expression program. Public Library of Science 2014-10-09 /pmc/articles/PMC4191881/ /pubmed/25299042 http://dx.doi.org/10.1371/journal.pcbi.1003845 Text en © 2014 Mauri, Klumpp http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mauri, Marco
Klumpp, Stefan
A Model for Sigma Factor Competition in Bacterial Cells
title A Model for Sigma Factor Competition in Bacterial Cells
title_full A Model for Sigma Factor Competition in Bacterial Cells
title_fullStr A Model for Sigma Factor Competition in Bacterial Cells
title_full_unstemmed A Model for Sigma Factor Competition in Bacterial Cells
title_short A Model for Sigma Factor Competition in Bacterial Cells
title_sort model for sigma factor competition in bacterial cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191881/
https://www.ncbi.nlm.nih.gov/pubmed/25299042
http://dx.doi.org/10.1371/journal.pcbi.1003845
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