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The propagation of perturbations in rewired bacterial gene networks
What happens to gene expression when you add new links to a gene regulatory network? To answer this question, we profile 85 network rewirings in E. coli. Here we report that concerted patterns of differential expression propagate from reconnected hub genes. The rewirings link promoter regions to dif...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703840/ https://www.ncbi.nlm.nih.gov/pubmed/26670742 http://dx.doi.org/10.1038/ncomms10105 |
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author | Baumstark, Rebecca Hänzelmann, Sonja Tsuru, Saburo Schaerli, Yolanda Francesconi, Mirko Mancuso, Francesco M. Castelo, Robert Isalan, Mark |
author_facet | Baumstark, Rebecca Hänzelmann, Sonja Tsuru, Saburo Schaerli, Yolanda Francesconi, Mirko Mancuso, Francesco M. Castelo, Robert Isalan, Mark |
author_sort | Baumstark, Rebecca |
collection | PubMed |
description | What happens to gene expression when you add new links to a gene regulatory network? To answer this question, we profile 85 network rewirings in E. coli. Here we report that concerted patterns of differential expression propagate from reconnected hub genes. The rewirings link promoter regions to different transcription factor and σ-factor genes, resulting in perturbations that span four orders of magnitude, changing up to ∼70% of the transcriptome. Importantly, factor connectivity and promoter activity both associate with perturbation size. Perturbations from related rewirings have more similar transcription profiles and a statistical analysis reveals ∼20 underlying states of the system, associating particular gene groups with rewiring constructs. We examine two large clusters (ribosomal and flagellar genes) in detail. These represent alternative global outcomes from different rewirings because of antagonism between these major cell states. This data set of systematically related perturbations enables reverse engineering and discovery of underlying network interactions. |
format | Online Article Text |
id | pubmed-4703840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47038402016-01-22 The propagation of perturbations in rewired bacterial gene networks Baumstark, Rebecca Hänzelmann, Sonja Tsuru, Saburo Schaerli, Yolanda Francesconi, Mirko Mancuso, Francesco M. Castelo, Robert Isalan, Mark Nat Commun Article What happens to gene expression when you add new links to a gene regulatory network? To answer this question, we profile 85 network rewirings in E. coli. Here we report that concerted patterns of differential expression propagate from reconnected hub genes. The rewirings link promoter regions to different transcription factor and σ-factor genes, resulting in perturbations that span four orders of magnitude, changing up to ∼70% of the transcriptome. Importantly, factor connectivity and promoter activity both associate with perturbation size. Perturbations from related rewirings have more similar transcription profiles and a statistical analysis reveals ∼20 underlying states of the system, associating particular gene groups with rewiring constructs. We examine two large clusters (ribosomal and flagellar genes) in detail. These represent alternative global outcomes from different rewirings because of antagonism between these major cell states. This data set of systematically related perturbations enables reverse engineering and discovery of underlying network interactions. Nature Publishing Group 2015-12-16 /pmc/articles/PMC4703840/ /pubmed/26670742 http://dx.doi.org/10.1038/ncomms10105 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) |
spellingShingle | Article Baumstark, Rebecca Hänzelmann, Sonja Tsuru, Saburo Schaerli, Yolanda Francesconi, Mirko Mancuso, Francesco M. Castelo, Robert Isalan, Mark The propagation of perturbations in rewired bacterial gene networks |
title | The propagation of perturbations in rewired bacterial gene networks |
title_full | The propagation of perturbations in rewired bacterial gene networks |
title_fullStr | The propagation of perturbations in rewired bacterial gene networks |
title_full_unstemmed | The propagation of perturbations in rewired bacterial gene networks |
title_short | The propagation of perturbations in rewired bacterial gene networks |
title_sort | propagation of perturbations in rewired bacterial gene networks |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4703840/ https://www.ncbi.nlm.nih.gov/pubmed/26670742 http://dx.doi.org/10.1038/ncomms10105 |
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