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Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting
Cellular decision‐making and environmental adaptation are dependent upon a heterogeneous response of gene expression to external cues. Heterogeneity arises in transcription from random switching between transcriptionally active and inactive states, resulting in bursts of RNA synthesis. Furthermore,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825209/ https://www.ncbi.nlm.nih.gov/pubmed/29476006 http://dx.doi.org/10.15252/msb.20177678 |
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author | Fritzsch, Christoph Baumgärtner, Stephan Kuban, Monika Steinshorn, Daria Reid, George Legewie, Stefan |
author_facet | Fritzsch, Christoph Baumgärtner, Stephan Kuban, Monika Steinshorn, Daria Reid, George Legewie, Stefan |
author_sort | Fritzsch, Christoph |
collection | PubMed |
description | Cellular decision‐making and environmental adaptation are dependent upon a heterogeneous response of gene expression to external cues. Heterogeneity arises in transcription from random switching between transcriptionally active and inactive states, resulting in bursts of RNA synthesis. Furthermore, the cellular state influences the competency of transcription, thereby globally affecting gene expression in a cell‐specific manner. We determined how external stimuli interplay with cellular state to modulate the kinetics of bursting. To this end, single‐cell dynamics of nascent transcripts were monitored at the endogenous estrogen‐responsive GREB1 locus. Stochastic modeling of gene expression implicated a two‐state promoter model in which the estrogen stimulus modulates the frequency of transcriptional bursting. The cellular state affects transcriptional dynamics by altering initiation and elongation kinetics and acts globally, as GREB1 alleles in the same cell correlate in their transcriptional output. Our results suggest that cellular state strongly affects the first step of the central dogma of gene expression, to promote heterogeneity in the transcriptional output of isogenic cells. |
format | Online Article Text |
id | pubmed-5825209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58252092018-02-28 Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting Fritzsch, Christoph Baumgärtner, Stephan Kuban, Monika Steinshorn, Daria Reid, George Legewie, Stefan Mol Syst Biol Articles Cellular decision‐making and environmental adaptation are dependent upon a heterogeneous response of gene expression to external cues. Heterogeneity arises in transcription from random switching between transcriptionally active and inactive states, resulting in bursts of RNA synthesis. Furthermore, the cellular state influences the competency of transcription, thereby globally affecting gene expression in a cell‐specific manner. We determined how external stimuli interplay with cellular state to modulate the kinetics of bursting. To this end, single‐cell dynamics of nascent transcripts were monitored at the endogenous estrogen‐responsive GREB1 locus. Stochastic modeling of gene expression implicated a two‐state promoter model in which the estrogen stimulus modulates the frequency of transcriptional bursting. The cellular state affects transcriptional dynamics by altering initiation and elongation kinetics and acts globally, as GREB1 alleles in the same cell correlate in their transcriptional output. Our results suggest that cellular state strongly affects the first step of the central dogma of gene expression, to promote heterogeneity in the transcriptional output of isogenic cells. John Wiley and Sons Inc. 2018-02-23 /pmc/articles/PMC5825209/ /pubmed/29476006 http://dx.doi.org/10.15252/msb.20177678 Text en © 2018 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Fritzsch, Christoph Baumgärtner, Stephan Kuban, Monika Steinshorn, Daria Reid, George Legewie, Stefan Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting |
title | Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting |
title_full | Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting |
title_fullStr | Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting |
title_full_unstemmed | Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting |
title_short | Estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting |
title_sort | estrogen‐dependent control and cell‐to‐cell variability of transcriptional bursting |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825209/ https://www.ncbi.nlm.nih.gov/pubmed/29476006 http://dx.doi.org/10.15252/msb.20177678 |
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