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A General Mechanism for Network-Dosage Compensation in Gene Circuits

Acar, Murat and Pando, Bernardo F. and Arnold, Frances H. and Elowitz, Michael B. and van Oudenaarden, Alexander (2010) A General Mechanism for Network-Dosage Compensation in Gene Circuits. Science, 329 (5999). pp. 1656-1660. ISSN 0036-8075. PMCID PMC3138731. doi:10.1126/science.1190544.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Arnold, Frances H.0000-0002-4027-364X
Elowitz, Michael B.0000-0002-1221-0967
Additional Information:© 2010 American Association for the Advancement of Science. Received 6 April 2010; accepted 9 August 2010. The authors would like to thank J. J. Collins, M. Thattai, and H. Youk for helpful discussions and/or comments on the manuscript. M.A. was supported by a fellowship grant from the Center for Biological Circuit Design at Caltech. B.F.P. and A.v.O were supported by grants from NIH and NSF. Work in the Elowitz laboratory was supported by the Packard Foundation, NSF, and NIH. Work in the Arnold laboratory was supported by NIH.
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Caltech Center for Biological Circuit DesignUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
Issue or Number:5999
PubMed Central ID:PMC3138731
Record Number:CaltechAUTHORS:20101011-132711462
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:20384
Deposited By: Tony Diaz
Deposited On:15 Nov 2010 20:24
Last Modified:08 Nov 2021 23:59

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