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Effects of promoter leakage on dynamics of gene expression

BACKGROUND: Quantitative analysis of simple molecular networks is an important step forward understanding fundamental intracellular processes. As network motifs occurring recurrently in complex biological networks, gene auto-regulatory circuits have been extensively studied but gene expression dynam...

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Detalles Bibliográficos
Autores principales: Huang, Lifang, Yuan, Zhanjiang, Liu, Peijiang, Zhou, Tianshou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384279/
https://www.ncbi.nlm.nih.gov/pubmed/25888718
http://dx.doi.org/10.1186/s12918-015-0157-z
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author Huang, Lifang
Yuan, Zhanjiang
Liu, Peijiang
Zhou, Tianshou
author_facet Huang, Lifang
Yuan, Zhanjiang
Liu, Peijiang
Zhou, Tianshou
author_sort Huang, Lifang
collection PubMed
description BACKGROUND: Quantitative analysis of simple molecular networks is an important step forward understanding fundamental intracellular processes. As network motifs occurring recurrently in complex biological networks, gene auto-regulatory circuits have been extensively studied but gene expression dynamics remain to be fully understood, e.g., how promoter leakage affects expression noise is unclear. RESULTS: In this work, we analyze a gene model with auto regulation, where the promoter is assumed to have one active state with highly efficient transcription and one inactive state with very lowly efficient transcription (termed as promoter leakage). We first derive the analytical distribution of gene product, and then analyze effects of promoter leakage on expression dynamics including bursting kinetics. Interestingly, we find that promoter leakage always reduces expression noise and that increasing the leakage rate tends to simplify phenotypes. In addition, higher leakage results in fewer bursts. CONCLUSIONS: Our results reveal the essential role of promoter leakage in controlling expression dynamics and further phenotype. Specifically, promoter leakage is a universal mechanism of reducing expression noise, controlling phenotypes in different environments and making the gene produce generate fewer bursts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-015-0157-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-43842792015-04-04 Effects of promoter leakage on dynamics of gene expression Huang, Lifang Yuan, Zhanjiang Liu, Peijiang Zhou, Tianshou BMC Syst Biol Research Article BACKGROUND: Quantitative analysis of simple molecular networks is an important step forward understanding fundamental intracellular processes. As network motifs occurring recurrently in complex biological networks, gene auto-regulatory circuits have been extensively studied but gene expression dynamics remain to be fully understood, e.g., how promoter leakage affects expression noise is unclear. RESULTS: In this work, we analyze a gene model with auto regulation, where the promoter is assumed to have one active state with highly efficient transcription and one inactive state with very lowly efficient transcription (termed as promoter leakage). We first derive the analytical distribution of gene product, and then analyze effects of promoter leakage on expression dynamics including bursting kinetics. Interestingly, we find that promoter leakage always reduces expression noise and that increasing the leakage rate tends to simplify phenotypes. In addition, higher leakage results in fewer bursts. CONCLUSIONS: Our results reveal the essential role of promoter leakage in controlling expression dynamics and further phenotype. Specifically, promoter leakage is a universal mechanism of reducing expression noise, controlling phenotypes in different environments and making the gene produce generate fewer bursts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12918-015-0157-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-21 /pmc/articles/PMC4384279/ /pubmed/25888718 http://dx.doi.org/10.1186/s12918-015-0157-z Text en © Huang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Huang, Lifang
Yuan, Zhanjiang
Liu, Peijiang
Zhou, Tianshou
Effects of promoter leakage on dynamics of gene expression
title Effects of promoter leakage on dynamics of gene expression
title_full Effects of promoter leakage on dynamics of gene expression
title_fullStr Effects of promoter leakage on dynamics of gene expression
title_full_unstemmed Effects of promoter leakage on dynamics of gene expression
title_short Effects of promoter leakage on dynamics of gene expression
title_sort effects of promoter leakage on dynamics of gene expression
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4384279/
https://www.ncbi.nlm.nih.gov/pubmed/25888718
http://dx.doi.org/10.1186/s12918-015-0157-z
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