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.
journal_name
Biophys Jjournal_title
Biophysical journalauthors
Murugan R,Kreiman Gdoi
10.1016/j.bpj.2011.08.005subject
Has Abstractpub_date
2011-09-21 00:00:00pages
1297-306issue
6eissn
0006-3495issn
1542-0086pii
S0006-3495(11)00946-5journal_volume
101pub_type
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