Direct observation of frequency modulated transcription in single cells using light activation

Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated...

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Autores principales: Larson, Daniel R, Fritzsch, Christoph, Sun, Liang, Meng, Xiuhau, Lawrence, David S, Singer, Robert H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2013
Materias:
Biophysics and Structural Biology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780543/
https://www.ncbi.nlm.nih.gov/pubmed/24069527
http://dx.doi.org/10.7554/eLife.00750
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author Larson, Daniel R
Fritzsch, Christoph
Sun, Liang
Meng, Xiuhau
Lawrence, David S
Singer, Robert H
author_facet Larson, Daniel R
Fritzsch, Christoph
Sun, Liang
Meng, Xiuhau
Lawrence, David S
Singer, Robert H
author_sort Larson, Daniel R
collection PubMed
description Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single steroid-responsive gene and follow dynamic synthesis of RNA from the activated locus. DOI: http://dx.doi.org/10.7554/eLife.00750.001
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spelling pubmed-37805432013-09-25 Direct observation of frequency modulated transcription in single cells using light activation Larson, Daniel R Fritzsch, Christoph Sun, Liang Meng, Xiuhau Lawrence, David S Singer, Robert H eLife Biophysics and Structural Biology Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single steroid-responsive gene and follow dynamic synthesis of RNA from the activated locus. DOI: http://dx.doi.org/10.7554/eLife.00750.001 eLife Sciences Publications, Ltd 2013-09-24 /pmc/articles/PMC3780543/ /pubmed/24069527 http://dx.doi.org/10.7554/eLife.00750 Text en http://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Biophysics and Structural Biology
Larson, Daniel R
Fritzsch, Christoph
Sun, Liang
Meng, Xiuhau
Lawrence, David S
Singer, Robert H
Direct observation of frequency modulated transcription in single cells using light activation
title Direct observation of frequency modulated transcription in single cells using light activation
title_full Direct observation of frequency modulated transcription in single cells using light activation
title_fullStr Direct observation of frequency modulated transcription in single cells using light activation
title_full_unstemmed Direct observation of frequency modulated transcription in single cells using light activation
title_short Direct observation of frequency modulated transcription in single cells using light activation
title_sort direct observation of frequency modulated transcription in single cells using light activation
topic Biophysics and Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3780543/
https://www.ncbi.nlm.nih.gov/pubmed/24069527
http://dx.doi.org/10.7554/eLife.00750
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