Letter abstract
Nature Genetics 40, 1493 - 1498 (2008)
Published online: 23 November 2008 | doi:10.1038/ng.281
Regulatory activity revealed by dynamic correlations in gene expression noise
Mary J Dunlop1, Robert Sidney Cox, III2, Joseph H Levine1, Richard M Murray1 & Michael B Elowitz2,3,4
Gene regulatory interactions are context dependent, active in some cellular states but not in others. Stochastic fluctuations, or 'noise', in gene expression propagate through active, but not inactive, regulatory links1, 2. Thus, correlations in gene expression noise could provide a noninvasive means to probe the activity states of regulatory links. However, global, 'extrinsic', noise sources generate correlations even without direct regulatory links. Here we show that single-cell time-lapse microscopy, by revealing time lags due to regulation, can discriminate between active regulatory connections and extrinsic noise. We demonstrate this principle mathematically, using stochastic modeling, and experimentally, using simple synthetic gene circuits. We then use this approach to analyze dynamic noise correlations in the galactose metabolism genes of Escherichia coli. We find that the CRP-GalS-GalE feed-forward loop is inactive in standard conditions but can become active in a GalR mutant. These results show how noise can help analyze the context dependence of regulatory interactions in endogenous gene circuits.
- Division of Engineering and Applied Science, California Institute of Technology 1200 E. California Blvd. M/C 114-96 Pasadena, California 91125, USA.
- Division of Biology, California Institute of Technology 1200 E. California Blvd. M/C 114-96 Pasadena, California 91125, USA.
- Department of Applied Physics, California Institute of Technology 1200 E. California Blvd. M/C 114-96 Pasadena, California 91125, USA.
- Howard Hughes Medical Institute, California Institute of Technology 1200 E. California Blvd. M/C 114-96 Pasadena, California 91125, USA.
Correspondence to: Michael B Elowitz2,3,4 e-mail: melowitz@caltech.edu
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