On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks
Name
Murugan-2011-On the Minimization.pdf
Size
1.75 MB
Format
Adobe PDF
Checksum (MD5)
cf00be273314ebdc3b77ed2256644bbe
Author(s)
Murugan, Rajamanickam
Kreiman, Gabriel
Date Issued
September 2011
Journal
Biophysical Journal
Publisher
Elsevier
Citation
Murugan, Rajamanickam, and Gabriel Kreiman. “On the Minimization of Fluctuations in the Response Times of Autoregulatory Gene Networks.” Biophysical Journal 101, no. 6 (September 2011): 1297–1306. © Biophysical Society
Version
Final published version
Abstract
The temporal dynamics of the concentrations of several proteins are tightly regulated, particularly for critical nodes 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.
MIT Department
McGovern Institute for Brain Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.bpj.2011.08.005
