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Biophys J, December 2000, p. 2944-2953, Vol. 79, No. 6

Fluctuations in Repressor Control: Thermodynamic Constraints on Stochastic Focusing

Otto G. Berg,* Johan Paulsson,dagger and Måns Ehrenbergdagger

 *Department of Molecular Evolution, Evolutionary Biology Centre, and  dagger Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, SE-75124 Uppsala, Sweden

The influence of fluctuations in molecule numbers on genetic control circuits has received considerable attention. The consensus has been that such fluctuations will make regulation less precise. In contrast, it has more recently been shown that signal fluctuations can sharpen the response in a regulated process by the principle of stochastic focusing (SF) (Paulsson et al., 2000, Proc. Natl. Acad. Sci. USA. 97:7148-7153). In many cases, the larger the fluctuations are, the sharper is the response. Here we investigate how fluctuations in repressor or corepressor numbers can improve the control of gene expression. Because SF is found to be constrained by detailed balance, this requires that the control loops contain driven processes out of equilibrium. Some simple and realistic out-of-equilibrium steps that will break detailed balance and make room for SF in such systems are discussed. We conclude that when the active repressors are controlled by corepressor molecules that display large ("coherent") number fluctuations or when corepressors can be irreversibly removed directly from promoter-bound repressors, the response in gene activity can become significantly sharper than without intrinsic noise. A simple experimental design to establish the possibility of SF for repressor control is suggested.

Biophys J, December 2000, p. 2944-2953, Vol. 79, No. 6
© 2000 by the Biophysical Society   0006-3495/00/12/2944/10  $2.00


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