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Fluctuations in repressor control: thermodynamic constraints on stochastic focusing
O G Berg1, J Paulsson, M Ehrenberg
1Department of Molecular Evolution, Evolutionary Biology Centre, Uppsala University, SE-75124 Uppsala, Sweden.
Biophysical Journal
|December 7, 2000
Summary
Fluctuations in molecule numbers can surprisingly sharpen gene expression control. Introducing out-of-equilibrium processes, like large corepressor fluctuations, enhances this effect, improving genetic regulation precision.
Area of Science:
- Systems Biology
- Molecular Biology
- Biophysics
Background:
- Genetic control circuits are influenced by molecular number fluctuations.
- Traditionally, these fluctuations were thought to decrease regulatory precision.
- Stochastic focusing (SF) demonstrates that signal fluctuations can enhance response sharpness.
Purpose of the Study:
- To investigate how repressor or corepressor number fluctuations improve gene expression control.
- To explore mechanisms for achieving SF in genetic regulation, particularly out-of-equilibrium processes.
Main Methods:
- Theoretical investigation of genetic control loops.
- Analysis of systems with driven processes out of equilibrium.
- Discussion of steps that break detailed balance to enable SF.
Main Results:
- SF requires control loops to operate out of equilibrium, breaking detailed balance.
- Large, coherent fluctuations in corepressor numbers can sharpen gene activity response.
- Irreversible removal of corepressors from promoters also enhances response sharpness.
Conclusions:
- Intrinsic noise, specifically large corepressor fluctuations or irreversible removal, can significantly sharpen gene expression control.
- Out-of-equilibrium processes are crucial for enabling stochastic focusing in genetic regulation.
- An experimental design is proposed to validate SF in repressor control systems.