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Nucleic Acids Research 2006 34(8):2455-2462; doi:10.1093/nar/gkl140
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Published online 9 May 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Article

Structure and function of negative feedback loops at the interface of genetic and metabolic networks

Sandeep Krishna, Anna M. C. Andersson, Szabolcs Semsey and Kim Sneppen*

Center for models of Life, Niels Bohr Institute Blegdamsvej 17, 2100 Copenhagen, Denmark

*To whom correspondence should be addressed. Tel: +45 353 25352; Fax: +45 353 25425; Email: sneppen{at}nbi.dk

Received February 15, 2006. Revised March 15, 2006. Accepted March 15, 2006.

The molecular network in an organism consists of transcription/translation regulation, protein–protein interactions/modifications and a metabolic network, together forming a system that allows the cell to respond sensibly to the multiple signal molecules that exist in its environment. A key part of this overall system of molecular regulation is therefore the interface between the genetic and the metabolic network. A motif that occurs very often at this interface is a negative feedback loop used to regulate the level of the signal molecules. In this work we use mathematical models to investigate the steady state and dynamical behaviour of different negative feedback loops. We show, in particular, that feedback loops where the signal molecule does not cause the dissociation of the transcription factor from the DNA respond faster than loops where the molecule acts by sequestering transcription factors off the DNA. We use three examples, the bet, mer and lac systems in Escherichia coli, to illustrate the behaviour of such feedback loops.


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