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On chaotic dynamics in transcription factors and the associated effects in differential gene regulation

The control of proteins by a transcription factor with periodically varying concentration exhibits intriguing dynamical behaviour. Even though it is accepted that transcription factors vary their dynamics in response to different situations, insight into how this affects downstream genes is lacking....

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Autores principales: Heltberg, Mathias L., Krishna, Sandeep, Jensen, Mogens H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325146/
https://www.ncbi.nlm.nih.gov/pubmed/30622249
http://dx.doi.org/10.1038/s41467-018-07932-1
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author Heltberg, Mathias L.
Krishna, Sandeep
Jensen, Mogens H.
author_facet Heltberg, Mathias L.
Krishna, Sandeep
Jensen, Mogens H.
author_sort Heltberg, Mathias L.
collection PubMed
description The control of proteins by a transcription factor with periodically varying concentration exhibits intriguing dynamical behaviour. Even though it is accepted that transcription factors vary their dynamics in response to different situations, insight into how this affects downstream genes is lacking. Here, we investigate how oscillations and chaotic dynamics in the transcription factor NF-κB can affect downstream protein production. We describe how it is possible to control the effective dynamics of the transcription factor by stimulating it with an oscillating ligand. We find that chaotic dynamics modulates gene expression and up-regulates certain families of low-affinity genes, even in the presence of extrinsic and intrinsic noise. Furthermore, this leads to an increase in the production of protein complexes and the efficiency of their assembly. Finally, we show how chaotic dynamics creates a heterogeneous population of cell states, and describe how this can be beneficial in multi-toxic environments.
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spelling pubmed-63251462019-01-10 On chaotic dynamics in transcription factors and the associated effects in differential gene regulation Heltberg, Mathias L. Krishna, Sandeep Jensen, Mogens H. Nat Commun Article The control of proteins by a transcription factor with periodically varying concentration exhibits intriguing dynamical behaviour. Even though it is accepted that transcription factors vary their dynamics in response to different situations, insight into how this affects downstream genes is lacking. Here, we investigate how oscillations and chaotic dynamics in the transcription factor NF-κB can affect downstream protein production. We describe how it is possible to control the effective dynamics of the transcription factor by stimulating it with an oscillating ligand. We find that chaotic dynamics modulates gene expression and up-regulates certain families of low-affinity genes, even in the presence of extrinsic and intrinsic noise. Furthermore, this leads to an increase in the production of protein complexes and the efficiency of their assembly. Finally, we show how chaotic dynamics creates a heterogeneous population of cell states, and describe how this can be beneficial in multi-toxic environments. Nature Publishing Group UK 2019-01-08 /pmc/articles/PMC6325146/ /pubmed/30622249 http://dx.doi.org/10.1038/s41467-018-07932-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Heltberg, Mathias L.
Krishna, Sandeep
Jensen, Mogens H.
On chaotic dynamics in transcription factors and the associated effects in differential gene regulation
title On chaotic dynamics in transcription factors and the associated effects in differential gene regulation
title_full On chaotic dynamics in transcription factors and the associated effects in differential gene regulation
title_fullStr On chaotic dynamics in transcription factors and the associated effects in differential gene regulation
title_full_unstemmed On chaotic dynamics in transcription factors and the associated effects in differential gene regulation
title_short On chaotic dynamics in transcription factors and the associated effects in differential gene regulation
title_sort on chaotic dynamics in transcription factors and the associated effects in differential gene regulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325146/
https://www.ncbi.nlm.nih.gov/pubmed/30622249
http://dx.doi.org/10.1038/s41467-018-07932-1
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