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Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks
Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation betwee...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Biophysical Society
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406374/ https://www.ncbi.nlm.nih.gov/pubmed/28445746 http://dx.doi.org/10.1016/j.bpj.2017.02.044 |
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author | Rowland, Michael A. Abdelzaher, Ahmed Ghosh, Preetam Mayo, Michael L. |
author_facet | Rowland, Michael A. Abdelzaher, Ahmed Ghosh, Preetam Mayo, Michael L. |
author_sort | Rowland, Michael A. |
collection | PubMed |
description | Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (≈20% for one crosstalk interaction) and remain dynamically modular. The likelihood that cross-linked FFLs are dynamically correlated increases monotonically with additional crosstalk, but is independent of the specific regulation type or connectivity of the interactions. Just one additional regulatory interaction is sufficient to drive the FFL dynamics to a statistically different state. Despite the potential for modularity between sparsely connected network motifs, Escherichia coli (E. coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs remains modular. A gene ontology analysis reveals that stress response processes are significantly overrepresented in the cross-linked motifs found within E. coli. Although the daunting complexity of biological networks affects the dynamical properties of individual network motifs, some resist and remain modular, seemingly insulated from extrinsic perturbations—an intriguing possibility for nature to consistently and reliably provide certain network functionalities wherever the need arise. |
format | Online Article Text |
id | pubmed-5406374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Biophysical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-54063742018-04-25 Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks Rowland, Michael A. Abdelzaher, Ahmed Ghosh, Preetam Mayo, Michael L. Biophys J Nucleic Acids and Genome Biophysics Network motifs, such as the feed-forward loop (FFL), introduce a range of complex behaviors to transcriptional regulatory networks, yet such properties are typically determined from their isolated study. We characterize the effects of crosstalk on FFL dynamics by modeling the cross regulation between two different FFLs and evaluate the extent to which these patterns occur in vivo. Analytical modeling suggests that crosstalk should overwhelmingly affect individual protein-expression dynamics. Counter to this expectation we find that entire FFLs are more likely than expected to resist the effects of crosstalk (≈20% for one crosstalk interaction) and remain dynamically modular. The likelihood that cross-linked FFLs are dynamically correlated increases monotonically with additional crosstalk, but is independent of the specific regulation type or connectivity of the interactions. Just one additional regulatory interaction is sufficient to drive the FFL dynamics to a statistically different state. Despite the potential for modularity between sparsely connected network motifs, Escherichia coli (E. coli) appears to favor crosstalk wherein at least one of the cross-linked FFLs remains modular. A gene ontology analysis reveals that stress response processes are significantly overrepresented in the cross-linked motifs found within E. coli. Although the daunting complexity of biological networks affects the dynamical properties of individual network motifs, some resist and remain modular, seemingly insulated from extrinsic perturbations—an intriguing possibility for nature to consistently and reliably provide certain network functionalities wherever the need arise. The Biophysical Society 2017-04-25 2017-04-25 /pmc/articles/PMC5406374/ /pubmed/28445746 http://dx.doi.org/10.1016/j.bpj.2017.02.044 Text en http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Nucleic Acids and Genome Biophysics Rowland, Michael A. Abdelzaher, Ahmed Ghosh, Preetam Mayo, Michael L. Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks |
title | Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks |
title_full | Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks |
title_fullStr | Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks |
title_full_unstemmed | Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks |
title_short | Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks |
title_sort | crosstalk and the dynamical modularity of feed-forward loops in transcriptional regulatory networks |
topic | Nucleic Acids and Genome Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406374/ https://www.ncbi.nlm.nih.gov/pubmed/28445746 http://dx.doi.org/10.1016/j.bpj.2017.02.044 |
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