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Engineering stability in gene networks by autoregulation

Abstract

The genetic and biochemical networks which underlie such things as homeostasis in metabolism and the developmental programs of living cells, must withstand considerable variations and random perturbations of biochemical parameters1,2,3. These occur as transient changes in, for example, transcription, translation, and RNA and protein degradation. The intensity and duration of these perturbations differ between cells in a population4. The unique state of cells, and thus the diversity in a population, is owing to the different environmental stimuli the individual cells experience and the inherent stochastic nature of biochemical processes (for example, refs 5 and 6). It has been proposed, but not demonstrated, that autoregulatory, negative feedback loops in gene circuits provide stability7, thereby limiting the range over which the concentrations of network components fluctuate. Here we have designed and constructed simple gene circuits consisting of a regulator and transcriptional repressor modules in Escherichia coli and we show the gain of stability produced by negative feedback.

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Figure 1: Stability properties of gene circuits.
Figure 2: Gene circuits and corresponding typical distributions of fluorescence intensities.
Figure 3: Variability in classical and autoregulatory systems.

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Acknowledgements

We thank H. Bujard for the plasmids; J. Rietdorf and R. Pepperkok for help with fluorescence microscopy; M. Diehl and D. Thieffry for discussions; and H. Domingues and R. Guerois for reading the manuscript. A.B. is supported by the Louis-Jeantet foundation.

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Correspondence to Attila Becskei.

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Becskei, A., Serrano, L. Engineering stability in gene networks by autoregulation. Nature 405, 590–593 (2000). https://doi.org/10.1038/35014651

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