Journal
SCIENCE
Volume 329, Issue 5999, Pages 1656-1660Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1190544
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Funding
- Center for Biological Circuit Design at Caltech
- NIH
- NSF
- Packard Foundation
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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.
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