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Dynamics of protein noise can distinguish between alternate sources of gene-expression variability
Within individual cells, two molecular processes have been implicated as sources of noise in gene expression: (i) Poisson fluctuations in mRNA abundance arising from random birth and death of individual mRNA transcripts or (ii) promoter fluctuations arising from stochastic promoter transitions betwe...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
European Molecular Biology Organization
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435505/ https://www.ncbi.nlm.nih.gov/pubmed/22929617 http://dx.doi.org/10.1038/msb.2012.38 |
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author | Singh, Abhyudai Razooky, Brandon S Dar, Roy D Weinberger, Leor S |
author_facet | Singh, Abhyudai Razooky, Brandon S Dar, Roy D Weinberger, Leor S |
author_sort | Singh, Abhyudai |
collection | PubMed |
description | Within individual cells, two molecular processes have been implicated as sources of noise in gene expression: (i) Poisson fluctuations in mRNA abundance arising from random birth and death of individual mRNA transcripts or (ii) promoter fluctuations arising from stochastic promoter transitions between different transcriptional states. Steady-state measurements of variance in protein levels are insufficient to discriminate between these two mechanisms, and mRNA single-molecule fluorescence in situ hybridization (smFISH) is challenging when cellular mRNA concentrations are high. Here, we present a perturbation method that discriminates mRNA birth/death fluctuations from promoter fluctuations by measuring transient changes in protein variance and that can operate in the regime of high molecular numbers. Conceptually, the method exploits the fact that transcriptional blockage results in more rapid increases in protein variability when mRNA birth/death fluctuations dominate over promoter fluctuations. We experimentally demonstrate the utility of this perturbation approach in the HIV-1 model system. Our results support promoter fluctuations as the primary noise source in HIV-1 expression. This study illustrates a relatively simple method that complements mRNA smFISH hybridization and can be used with existing GFP-tagged libraries to include or exclude alternate sources of noise in gene expression. |
format | Online Article Text |
id | pubmed-3435505 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | European Molecular Biology Organization |
record_format | MEDLINE/PubMed |
spelling | pubmed-34355052012-09-07 Dynamics of protein noise can distinguish between alternate sources of gene-expression variability Singh, Abhyudai Razooky, Brandon S Dar, Roy D Weinberger, Leor S Mol Syst Biol Report Within individual cells, two molecular processes have been implicated as sources of noise in gene expression: (i) Poisson fluctuations in mRNA abundance arising from random birth and death of individual mRNA transcripts or (ii) promoter fluctuations arising from stochastic promoter transitions between different transcriptional states. Steady-state measurements of variance in protein levels are insufficient to discriminate between these two mechanisms, and mRNA single-molecule fluorescence in situ hybridization (smFISH) is challenging when cellular mRNA concentrations are high. Here, we present a perturbation method that discriminates mRNA birth/death fluctuations from promoter fluctuations by measuring transient changes in protein variance and that can operate in the regime of high molecular numbers. Conceptually, the method exploits the fact that transcriptional blockage results in more rapid increases in protein variability when mRNA birth/death fluctuations dominate over promoter fluctuations. We experimentally demonstrate the utility of this perturbation approach in the HIV-1 model system. Our results support promoter fluctuations as the primary noise source in HIV-1 expression. This study illustrates a relatively simple method that complements mRNA smFISH hybridization and can be used with existing GFP-tagged libraries to include or exclude alternate sources of noise in gene expression. European Molecular Biology Organization 2012-08-28 /pmc/articles/PMC3435505/ /pubmed/22929617 http://dx.doi.org/10.1038/msb.2012.38 Text en Copyright © 2012, EMBO and Macmillan Publishers Limited https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission. |
spellingShingle | Report Singh, Abhyudai Razooky, Brandon S Dar, Roy D Weinberger, Leor S Dynamics of protein noise can distinguish between alternate sources of gene-expression variability |
title | Dynamics of protein noise can distinguish between alternate sources of gene-expression variability |
title_full | Dynamics of protein noise can distinguish between alternate sources of gene-expression variability |
title_fullStr | Dynamics of protein noise can distinguish between alternate sources of gene-expression variability |
title_full_unstemmed | Dynamics of protein noise can distinguish between alternate sources of gene-expression variability |
title_short | Dynamics of protein noise can distinguish between alternate sources of gene-expression variability |
title_sort | dynamics of protein noise can distinguish between alternate sources of gene-expression variability |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435505/ https://www.ncbi.nlm.nih.gov/pubmed/22929617 http://dx.doi.org/10.1038/msb.2012.38 |
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