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Published online on December 15, 2005, 10.1073/pnas.0505231102
PNAS | December 27, 2005 | vol. 102 | no. 52 | 19103-19108


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MICROBIOLOGY
The global transcriptional regulatory network for metabolism in Escherichia coli exhibits few dominant functional states

Christian L. Barrett, Christopher D. Herring, Jennifer L. Reed, and Bernhard O. Palsson *

Bioengineering Department, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412

Edited by Philip P. Green, University of Washington School of Medicine, Seattle, WA and approved November 1, 2005 (received for review June 24, 2005)

A principal aim of systems biology is to develop in silico models of whole cells or cellular processes that explain and predict observable cellular phenotypes. Here, we use a model of a genome-scale reconstruction of the integrated metabolic and transcriptional regulatory networks for Escherichia coli, composed of 1,010 gene products, to assess the properties of all functional states computed in 15,580 different growth environments. The set of all functional states of the integrated network exhibits a discernable structure that can be visualized in 3-dimensional space, showing that the transcriptional regulatory network governing metabolism in E. coli responds primarily to the available electron acceptor and the presence of glucose as the carbon source. This result is consistent with recently published experimental data. The observation that a complex network composed of 1,010 genes is organized to achieve few dominant modes demonstrates the utility of the systems approach for consolidating large amounts of genome-scale molecular information about a genome and its regulation to elucidate an organism's preferred environments and functional capabilities.

systems biology | transcriptional regulation


Author contributions: C.L.B. designed research; C.L.B. and C.D.H. performed research; C.L.B. and C.D.H. analyzed data; C.L.B. and B.O.P. wrote the paper; and J.L.R. reconstructed the organism.

Conflict of interest statement: University of California at San Diego has a related patent application (U.S. Patent Application 20040072723) that has been licensed.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviation: TF, transcription factor.

* To whom correspondence should be addressed. E-mail: palsson{at}ucsd.edu.

© 2005 by The National Academy of Sciences of the USA


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