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Science. 2010 Sep 24;329(5999):1656-60. doi: 10.1126/science.1190544.

A general mechanism for network-dosage compensation in gene circuits.

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  • 1Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. acar@caltech.edu

Abstract

Coping with variations in network dosage is crucial for maintaining optimal function in gene networks. We explored how network structure facilitates network-level dosage compensation. By using the yeast galactose network as a model, we combinatorially deleted one of the two copies of its four regulatory genes and found that network activity was robust to the change in network dosage. A mathematical analysis revealed that a two-component genetic circuit with elements of opposite regulatory activity (activator and inhibitor) constitutes a minimal requirement for network-dosage invariance. Specific interaction topologies and a one-to-one interaction stoichiometry between the activating and inhibiting agents were additional essential elements facilitating dosage invariance. This mechanism of network-dosage invariance could represent a general design for gene network structure in cells.

PMID:
20929850
[PubMed - indexed for MEDLINE]
PMCID:
PMC3138731
Free PMC Article

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