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Short Residence Times of DNA-Bound Transcription Factors Can Reduce Gene Expression Noise and Increase the Transmission of Information in a Gene Regulation System

Gene expression noise is not just ubiquitous but also variable, and we still do not understand some of the most elementary factors that affect it. Among them is the residence time of a transcription factor (TF) on DNA, the mean time that a DNA-bound TF remains bound. Here, we use a stochastic model...

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Autores principales: Azpeitia, Eugenio, Wagner, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198700/
https://www.ncbi.nlm.nih.gov/pubmed/32411721
http://dx.doi.org/10.3389/fmolb.2020.00067
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author Azpeitia, Eugenio
Wagner, Andreas
author_facet Azpeitia, Eugenio
Wagner, Andreas
author_sort Azpeitia, Eugenio
collection PubMed
description Gene expression noise is not just ubiquitous but also variable, and we still do not understand some of the most elementary factors that affect it. Among them is the residence time of a transcription factor (TF) on DNA, the mean time that a DNA-bound TF remains bound. Here, we use a stochastic model of transcriptional regulation to study how residence time affects the gene expression noise that arises when a TF induces gene expression. We find that the effect of residence time on gene expression noise depends on the TF’s concentration and its affinity to DNA, which determine the level of induction of the gene. At high levels of induction, residence time has no effect on gene expression noise. However, as the level of induction decreases, short residence times reduce gene expression noise. The reason is that fast on-off TF binding dynamics prevent long periods where proteins are predominantly synthesized or degraded, which can cause excessive fluctuations in gene expression. As a consequence, short residence times can help a gene regulation system acquire information about the cellular environment it operates in. Our predictions are consistent with the observation that experimentally measured residence times are usually modest and lie between seconds to minutes.
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spelling pubmed-71987002020-05-14 Short Residence Times of DNA-Bound Transcription Factors Can Reduce Gene Expression Noise and Increase the Transmission of Information in a Gene Regulation System Azpeitia, Eugenio Wagner, Andreas Front Mol Biosci Molecular Biosciences Gene expression noise is not just ubiquitous but also variable, and we still do not understand some of the most elementary factors that affect it. Among them is the residence time of a transcription factor (TF) on DNA, the mean time that a DNA-bound TF remains bound. Here, we use a stochastic model of transcriptional regulation to study how residence time affects the gene expression noise that arises when a TF induces gene expression. We find that the effect of residence time on gene expression noise depends on the TF’s concentration and its affinity to DNA, which determine the level of induction of the gene. At high levels of induction, residence time has no effect on gene expression noise. However, as the level of induction decreases, short residence times reduce gene expression noise. The reason is that fast on-off TF binding dynamics prevent long periods where proteins are predominantly synthesized or degraded, which can cause excessive fluctuations in gene expression. As a consequence, short residence times can help a gene regulation system acquire information about the cellular environment it operates in. Our predictions are consistent with the observation that experimentally measured residence times are usually modest and lie between seconds to minutes. Frontiers Media S.A. 2020-04-28 /pmc/articles/PMC7198700/ /pubmed/32411721 http://dx.doi.org/10.3389/fmolb.2020.00067 Text en Copyright © 2020 Azpeitia and Wagner. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Azpeitia, Eugenio
Wagner, Andreas
Short Residence Times of DNA-Bound Transcription Factors Can Reduce Gene Expression Noise and Increase the Transmission of Information in a Gene Regulation System
title Short Residence Times of DNA-Bound Transcription Factors Can Reduce Gene Expression Noise and Increase the Transmission of Information in a Gene Regulation System
title_full Short Residence Times of DNA-Bound Transcription Factors Can Reduce Gene Expression Noise and Increase the Transmission of Information in a Gene Regulation System
title_fullStr Short Residence Times of DNA-Bound Transcription Factors Can Reduce Gene Expression Noise and Increase the Transmission of Information in a Gene Regulation System
title_full_unstemmed Short Residence Times of DNA-Bound Transcription Factors Can Reduce Gene Expression Noise and Increase the Transmission of Information in a Gene Regulation System
title_short Short Residence Times of DNA-Bound Transcription Factors Can Reduce Gene Expression Noise and Increase the Transmission of Information in a Gene Regulation System
title_sort short residence times of dna-bound transcription factors can reduce gene expression noise and increase the transmission of information in a gene regulation system
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198700/
https://www.ncbi.nlm.nih.gov/pubmed/32411721
http://dx.doi.org/10.3389/fmolb.2020.00067
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