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Nitzan Rosenfeld,1*Jonathan W. Young,3Uri Alon,1Peter S. Swain,2*Michael B. Elowitz3
The quantitative relation between transcription factor concentrationsand the rate of protein production from downstream genes iscentral to the function of genetic networks. Here we show thatthis relation, which we call the gene regulation function (GRF),fluctuates dynamically in individual living cells, thereby limitingthe accuracy with which transcriptional genetic circuits cantransfer signals. Using fluorescent reporter genes and fusionproteins, we characterized the bacteriophage lambda promoterPR in Escherichia coli. A novel technique based on binomialerrors in protein partitioning enabled calibration of in vivobiochemical parameters in molecular units. We found that proteinproduction rates fluctuate over a time scale of about one cellcycle, while intrinsic noise decays rapidly. Thus, biochemicalparameters, noise, and slowly varying cellular states togetherdetermine the effective single-cell GRF. These results can forma basis for quantitative modeling of natural gene circuits andfor design of synthetic ones.
1 Departments of Molecular Cell Biology and Physics of Complex Systems, Weizmann Institute of Science, Rehovot, 76100, Israel. 2 Centre for Non-linear Dynamics, Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montréal, Québec, Canada, H3G 1Y6. 3 Division of Biology and Department of Applied Physics, Caltech, Pasadena, CA 91125, USA.
* These authors contributed equally to this work
To whom correspondence should be addressed. E-mail: melowitz{at}caltech.edu
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