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Published October 30, 2009 | Supplemental Material
Journal Article Open

Architecture-Dependent Noise Discriminates Functionally Analogous Differentiation Circuits


Gene regulatory circuits with different architectures (patterns of regulatory interactions) can generate similar dynamics. This raises the question of why a particular circuit architecture is selected to implement a given cellular process. To investigate this problem, we compared the Bacillus subtilis circuit that regulates differentiation into the competence state to an engineered circuit with an alternative architecture (SynEx) in silico and in vivo. Time-lapse microscopy measurements showed that SynEx cells generated competence dynamics similar to native cells and reconstituted the physiology of differentiation. However, architectural differences between the circuits altered the dynamic distribution of stochastic fluctuations (noise) during circuit operation. This distinction in noise causes functional differences between the circuits by selectively controlling the timing of competence episodes and response of the system to various DNA concentrations. These results reveal a tradeoff between temporal precision and physiological response range that is controlled by distinct noise characteristics of alternative circuit architectures.

Additional Information

© 2009 Elsevier Inc. Received 1 April 2009; revised 6 June 2009; accepted 21 July 2009. Published online: October 22, 2009. Available online 22 October 2009. Supplemental Data include Supplemental Experimental Procedures, 17 figures, and seven tables and can be found with this article online at http://www.cell.com/supplemental/S0092-8674(09)01033-2. We thank Steve Altschuler, Robin Hiesinger, Rama Ranganathan, Michael Rosen, Elliott Ross, Katherine Suel, and Lani Wu for critical reading of this manuscript and helpful discussions. We also thank Alma Alvarado of the Suel laboratory for technical assistance. The authors acknowledge the Texas Advanced Computing Center at University of Texas, Austin, for providing computing resources. M.T. is supported by National Institutes of Health grant K25 GM071957. J.G.-O. acknowledges financial support from Ministerio de Ciencia e Innovacion (Spain, project ORDEN and I3 program) and from the European Commission (project GABA). This work was supported by research grants to G.M.S. by the Welch Foundation (I-1674) and the James S. McDonnell Foundation (220020141). G.M.S. is a W.W. Caruth Jr. Scholar of Biomedical Research. This work is dedicated to the memory of Merdol and Nursxat Suel.

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Supplemental Material - Cagatay2009p6362Cell_supp.pdf


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