A bottom-up approach to gene regulation

Nicholas J. Guido, Xiao Wang, David Adalsteinsson, David McMillen, Jeff Hasty, Charles R. Cantor, Timothy C. Elston, J. J. Collins

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

The ability to construct synthetic gene networks enables experimental investigations of deliberately simplified systems that can be compared to qualitative and quantitative models1-23. If simple, well-characterized modules can be coupled together into more complex networks with behaviour that can be predicted from that of the individual components, we may begin to build an understanding of cellular regulatory processes from the 'bottom up'. Here we have engineered a promoter to allow simultaneous repression and activation of gene expression in Escherichia coli. We studied its behaviour in synthetic gene networks under increasingly complex conditions: unregulated, repressed, activated, and simultaneously repressed and activated. We develop a stochastic model that quantitatively captures the means and distributions of the expression from the engineered promoter of this modular system, and show that the model can be extended and used to accurately predict the in vivo behaviour of the network when it is expanded to include positive feedback. The model also reveals the counterintuitive prediction that noise in protein expression levels can increase upon arrest of cell growth and division, which we confirm experimentally. This work shows that the properties of regulatory subsystems can be used to predict the behaviour of larger, more complex regulatory networks, and that this bottom-up approach can provide insights into gene regulation.

Original languageEnglish (US)
Pages (from-to)856-860
Number of pages5
JournalNature
Volume439
Issue number7078
DOIs
StatePublished - Feb 16 2006
Externally publishedYes

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Synthetic Genes
Gene Regulatory Networks
Cell Division
Genes
Noise
Escherichia coli
Gene Expression
Growth
Proteins

ASJC Scopus subject areas

  • General

Cite this

Guido, N. J., Wang, X., Adalsteinsson, D., McMillen, D., Hasty, J., Cantor, C. R., ... Collins, J. J. (2006). A bottom-up approach to gene regulation. Nature, 439(7078), 856-860. https://doi.org/10.1038/nature04473

A bottom-up approach to gene regulation. / Guido, Nicholas J.; Wang, Xiao; Adalsteinsson, David; McMillen, David; Hasty, Jeff; Cantor, Charles R.; Elston, Timothy C.; Collins, J. J.

In: Nature, Vol. 439, No. 7078, 16.02.2006, p. 856-860.

Research output: Contribution to journalArticle

Guido, NJ, Wang, X, Adalsteinsson, D, McMillen, D, Hasty, J, Cantor, CR, Elston, TC & Collins, JJ 2006, 'A bottom-up approach to gene regulation', Nature, vol. 439, no. 7078, pp. 856-860. https://doi.org/10.1038/nature04473
Guido NJ, Wang X, Adalsteinsson D, McMillen D, Hasty J, Cantor CR et al. A bottom-up approach to gene regulation. Nature. 2006 Feb 16;439(7078):856-860. https://doi.org/10.1038/nature04473
Guido, Nicholas J. ; Wang, Xiao ; Adalsteinsson, David ; McMillen, David ; Hasty, Jeff ; Cantor, Charles R. ; Elston, Timothy C. ; Collins, J. J. / A bottom-up approach to gene regulation. In: Nature. 2006 ; Vol. 439, No. 7078. pp. 856-860.
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