On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks
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https://doi.org/10.1016/j.bpj.2011.08.005Metadata
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Murugan, Rajamanickam, and Gabriel Kreiman. 2011. “On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks.” Biophysical Journal 101 (6) (September): 1297–1306. doi:10.1016/j.bpj.2011.08.005.Abstract
The temporal dynamics of the concentrations of several proteins are tightly regulated, particularly for criticalnodes in biological networks such as transcription factors. An important mechanism to control transcription factor levels is
through autoregulatory feedback loops where the protein can bind its own promoter. Here we use theoretical tools and computational
simulations to further our understanding of transcription-factor autoregulatory loops. We show that the stochastic
dynamics of feedback and mRNA synthesis can significantly influence the speed of response of autoregulatory genetic networks
toward external stimuli. The fluctuations in the response-times associated with the accumulation of the transcription factor in the
presence of negative or positive autoregulation can be minimized by confining the ratio of mRNA/protein lifetimes within 1:10.
This predicted range of mRNA/protein lifetime agrees with ranges observed empirically in prokaryotes and eukaryotes. The
theory can quantitatively and systematically account for the influence of regulatory element binding and unbinding dynamics
on the transcription-factor concentration rise-times. The simulation results are robust against changes in several system parameters
of the gene expression machinery.
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