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Published on: November 12, 2012
Exploring the behavior of small eukaryotic gene networks.
Frank J Bruggeman1, Ionela Oancea, Roel van Driel
1Molecular Cell Physiology, Vrije Universiteit, De Boelelaan 1087, 1081 HV, Amsterdam, The Netherlands. Frank.Bruggeman@falw.vu.nl
Journal of Theoretical Biology
|April 25, 2008
Summary
Gene clusters regulate gene activity through epigenetic mechanisms. This study models how interacting gene clusters generate multiple steady states and mimic cellular differentiation dynamics.
Area of Science:
- Genomics
- Systems Biology
- Epigenetics
Background:
- Higher eukaryotes exhibit genome organization with functionally related gene clusters.
- Gene activity within clusters is regulated hierarchically at local and global levels.
- Epigenetic status (permissive or silenced) dictates gene activation by transcription factors.
Purpose of the Study:
- To explore the functional consequences of gene clusters in gene networks.
- To investigate the behavior of mutually inhibiting gene clusters.
- To model how gene clusters can generate complex temporal dynamics.
Main Methods:
- Analysis of genome organization in higher eukaryotes.
- Modeling the steady-state behavior of two mutually inhibiting gene clusters.
- Simulation of a gene cluster module comprising a signal transduction network and a transcription factor.
Main Results:
- Mutually inhibiting gene clusters exhibit multiple steady states.
- A gene cluster module can generate temporal dynamics resembling cellular differentiation.
- The module demonstrates transient signal sensitivity and irreversible decision-making (hysteresis).
Conclusions:
- Gene clusters play a crucial role in complex gene network functioning.
- Epigenetic regulation of gene clusters allows for versatile cellular responses.
- Modeling gene clusters provides insights into mechanisms of cellular differentiation and commitment.
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