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Title: Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks

Abstract

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 ofmore » 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.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE; US Army
OSTI Identifier:
1376987
Alternate Identifier(s):
OSTI ID: 1623638
Grant/Contract Number:  
SC0014664
Resource Type:
Published Article
Journal Name:
Biophysical Journal
Additional Journal Information:
Journal Name: Biophysical Journal Journal Volume: 112 Journal Issue: 8; Journal ID: ISSN 0006-3495
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biophysics

Citation Formats

Rowland, Michael A., Abdelzaher, Ahmed, Ghosh, Preetam, and Mayo, Michael L.. Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks. United States: N. p., 2017. Web. https://doi.org/10.1016/j.bpj.2017.02.044.
Rowland, Michael A., Abdelzaher, Ahmed, Ghosh, Preetam, & Mayo, Michael L.. Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks. United States. https://doi.org/10.1016/j.bpj.2017.02.044
Rowland, Michael A., Abdelzaher, Ahmed, Ghosh, Preetam, and Mayo, Michael L.. Sat . "Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks". United States. https://doi.org/10.1016/j.bpj.2017.02.044.
@article{osti_1376987,
title = {Crosstalk and the Dynamical Modularity of Feed-Forward Loops in Transcriptional Regulatory Networks},
author = {Rowland, Michael A. and Abdelzaher, Ahmed and Ghosh, Preetam and Mayo, Michael L.},
abstractNote = {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.},
doi = {10.1016/j.bpj.2017.02.044},
journal = {Biophysical Journal},
number = 8,
volume = 112,
place = {United States},
year = {2017},
month = {4}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1016/j.bpj.2017.02.044

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