Cited by 109Gene Regulatory Network AnalysisDevelopmental Biology and Gene RegulationGenomics and Chromatin Dynamics

Modeling the dynamics of transcriptional gene regulatory networks for animal development

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Ben-Tabou de-Leon, Smadar, Davidson, Eric H.·2009·Developmental Biology

Abstract

The dynamic process of cell fate specification is regulated by networks of regulatory genes. The architecture of the network defines the temporal order of specification events. To understand the dynamic control of the developmental process, the kinetics of mRNA and protein synthesis and the response of the cis-regulatory modules to transcription factor concentration must be considered. Here we review mathematical models for mRNA and protein synthesis kinetics which are based on experimental measurements of the rates of the relevant processes. The model comprises the response functions of cis-regulatory modules to their transcription factor inputs, by incorporating binding site occupancy and its dependence on biologically measurable quantities. We use this model to simulate gene expression, to distinguish between cis-regulatory execution of "AND" and "OR" logic functions, rationalize the oscillatory behavior of certain transcriptional auto-repressors and to show how linked subcircuits can be dealt with. Model simulations display the effects of mutation of binding sites, or perturbation of upstream gene expression. The model is a generally useful tool for understanding gene regulation and the dynamics of cell fate specification.

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Crossref · 10.1016/j.ydbio.2008.10.043

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  • The estimated maximal translation rate constant in sea urchin embryos is 140 copies / (mRNA*h).

    “Based on Davidson and co-workers the estimated maximal translation rate constant in sea urchin embryos is 140 copies / (mRNA*h) 1 which is surprisingly close to the prediction of our model for mouse fibroblasts.”

    From Global quantification of mammalian gene expression control (2011) · cites this paper as [1]

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Authors
Ben-Tabou de-Leon, S., & Davidson, E. H.
Affiliations
California Institute of Technology (US)
Corresponding author
Davidson, Eric H.
Venue
Developmental Biology
Publisher
Elsevier BV
Published
2009-01
Volume
325
Issue
2
Pages
317-328
ISSN
0012-1606 (ISSN-L)
OpenAlex
W2120009112
Cited by
99
References
106
Citations by year
2025: 1 · 2024: 8 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 9 · 2016: 6 · 2015: 10 · 2014: 3 · 2013: 6 · 2012: 6
FWCI
0.64
Type
journal article
Language
en
Open access
Locations
  • Developmental Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM 61005, R01GM061005)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
cell fate specification, animal development, protein synthesis kinetics, cis-regulatory modules, response functions, gene expression oscillations, binding site mutations, mathematical modeling of gene regulation
MeSH terms
Animals, Binding Sites, Biological Clocks, DNA-Binding Proteins, Genes, Regulator, Kinetics, Models, Genetic, RNA, Messenger, Transcription Factors, Transcription, Genetic, Protein Biosynthesis, Gene Expression Regulation, Developmental, Gene Regulatory Networks

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