Cargando…

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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Fritzsch, Christoph, Baumgärtner, Stephan, Kuban, Monika, Steinshorn, Daria, Reid, George, Legewie, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
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
_version_ 1783302165455962112
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
work_keys_str_mv AT fritzschchristoph estrogendependentcontrolandcelltocellvariabilityoftranscriptionalbursting
AT baumgartnerstephan estrogendependentcontrolandcelltocellvariabilityoftranscriptionalbursting
AT kubanmonika estrogendependentcontrolandcelltocellvariabilityoftranscriptionalbursting
AT steinshorndaria estrogendependentcontrolandcelltocellvariabilityoftranscriptionalbursting
AT reidgeorge estrogendependentcontrolandcelltocellvariabilityoftranscriptionalbursting
AT legewiestefan estrogendependentcontrolandcelltocellvariabilityoftranscriptionalbursting