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Fitting structure to function in gene regulatory networks.

Ellen V Rothenberg1

  • 1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA. evroth@its.caltech.edu.

History and Philosophy of the Life Sciences
|October 18, 2017
PubMed
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Gene regulatory networks orchestrate development, but operate under different rules across species and life stages. Key differences in transcription factor dynamics and cellular history shape developmental trajectories.

Area of Science:

  • Developmental Biology
  • Systems Biology
  • Genetics

Background:

  • Transcriptional regulation cascades drive development, with gene regulatory networks (GRNs) integrating transcription factors (TFs) to control gene expression.
  • GRNs exhibit context-specific rules influencing network node kinetics, synchronicity, and logic.

Purpose of the Study:

  • To contrast GRN rule variations in distinct developmental systems.
  • To identify differences in TF dosage dependence, repression impacts, and regulatory history effects.

Main Methods:

  • Comparative analysis of GRNs in early embryonic development (flies, sea urchins) and adult mammalian hematopoiesis.
  • Examination of TF dosage, repression, and cellular regulatory history impacts on genome accessibility.
Keywords:
Boolean modelingChromatin accessibilityDevelopmental plasticityNetwork topologyT lymphocyte developmentTranscriptional regulation

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Main Results:

  • Significant differences observed in TF dosage dependence and repression efficacy between model organisms and mammalian systems.
  • Cellular regulatory history profoundly impacts genome accessibility in a context-dependent manner.

Conclusions:

  • Developmental GRNs are not universal, with distinct rules optimizing evolutionary needs.
  • Understanding these context-specific rules is crucial for accurate modeling of developmental mechanisms.