Cited by 185Gene Regulatory Network AnalysisNeural dynamics and brain functionAdvanced Differential Equations and Dynamical Systems

Frequency selectivity, multistability, and oscillations emerge from models of genetic regulatory systems

Smolen, Paul, Baxter, Douglas A., Byrne, John H.·1998·American Journal of Physiology-Cell Physiology

Abstract

To examine the capability of genetic regulatory systems for complex dynamic activity, we developed simple kinetic models that incorporate known features of these systems. These include autoregulation and stimulus-dependent phosphorylation of transcription factors (TFs), dimerization of TFs, crosstalk, and feedback. The simplest model manifested multiple stable steady states, and brief perturbations could switch the model between these states. Such transitions might explain, for example, how a brief pulse of hormone or neurotransmitter could elicit a long-lasting cellular response. In slightly more complex models, oscillatory regimes were identified. The addition of competition between activating and repressing TFs provided a plausible explanation for optimal stimulus frequencies that give maximal transcription. Such optimal frequencies are suggested by recent experiments comparing training paradigms for long-term memory formation and examining changes in mRNA levels in repetitively stimulated cultured cells. In general, the computational approach illustrated here, combined with appropriate experiments, provides a conceptual framework for investigating the function of genetic regulatory systems.

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Crossref · 10.1152/ajpcell.1998.274.2.c531

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  • Computational simulations have supported the plausibility of a mechanism based on differential phosphorylation of dCREB2 isoforms, but it has not been validated empirically.

    “Computational simulations have supported the plausibility of this mechanism65, but it has not been validated empirically.”

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Authors
Smolen, P., Baxter, D. A., & Byrne, J. H.
Affiliations
The University of Texas Health Science Center at Houston (US)
Venue
American Journal of Physiology-Cell Physiology
Published
1998-02-01
Volume
274
Issue
2
Pages
C531-C542
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
OpenAlex
W2167176119
Cited by
185
References
46
Citations by year
2026: 3 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 8 · 2021: 4 · 2020: 6 · 2019: 9 · 2018: 14 · 2017: 7 · 2016: 11 · 2015: 4 · 2014: 7 · 2013: 5 · 2012: 7
FWCI
0.28
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k05mh000649-09)
  • National Institute of Mental Health (K05 MH00649)
  • National Institute of Neurological Disorders and Stroke (T32 NS 07373, T32NS007373)
  • National Center for Research Resources (R01RR11626, R01RR011626)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
  • Physical Sciences › Mathematics › Geometry and Topology › Advanced Differential Equations and Dynamical Systems
Keywords
frequency selectivity, multistability, oscillations, autoregulation, transcription factor phosphorylation, transcription factor dimerization, crosstalk, feedback, long-term memory formation, kinetic model
MeSH terms
Animals, Gene Expression Regulation, Genes, Regulator, Homeostasis, Humans, Models, Genetic, Transcription Factors, Dimerization

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