4.8 Article

Motifs emerge from function in model gene regulatory networks

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1109435108

Keywords

essential interactions; genetic switch; transcription factors

Funding

  1. Polish Ministry of Science [N N202 229137]
  2. European Regional Development Fund [MPD/2009/6]

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Gene regulatory networks allow the control of gene expression patterns in living cells. The study of network topology has revealed that certain subgraphs of interactions or motifs appear at anomalously high frequencies. We ask here whether this phenomenon may emerge because of the functions carried out by these networks. Given a framework for describing regulatory interactions and dynamics, we consider in the space of all regulatory networks those that have prescribed functional capabilities. Markov Chain Monte Carlo sampling is then used to determine how these functional networks lead to specific motif statistics in the interactions. In the case where the regulatory networks are constrained to exhibit multistability, we find a high frequency of gene pairs that are mutually inhibitory and self-activating. In contrast, networks constrained to have periodic gene expression patterns (mimicking for instance the cell cycle) have a high frequency of bifan-like motifs involving four genes with at least one activating and one inhibitory interaction.

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