Extending the dynamic range of transcription factor action by translational regulation

T.R. Sokolowski, A. Walczak, W. Bialek, G. Tkacik, Physical Review E Statistical Nonlinear and Soft Matter Physics 93 (2016).


Journal Article | Published | English
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Abstract
A crucial step in the regulation of gene expression is binding of transcription factor (TF) proteins to regulatory sites along the DNA. But transcription factors act at nanomolar concentrations, and noise due to random arrival of these molecules at their binding sites can severely limit the precision of regulation. Recent work on the optimization of information flow through regulatory networks indicates that the lower end of the dynamic range of concentrations is simply inaccessible, overwhelmed by the impact of this noise. Motivated by the behavior of homeodomain proteins, such as the maternal morphogen Bicoid in the fruit fly embryo, we suggest a scheme in which transcription factors also act as indirect translational regulators, binding to the mRNA of other regulatory proteins. Intuitively, each mRNA molecule acts as an independent sensor of the input concentration, and averaging over these multiple sensors reduces the noise. We analyze information flow through this scheme and identify conditions under which it outperforms direct transcriptional regulation. Our results suggest that the dual role of homeodomain proteins is not just a historical accident, but a solution to a crucial physics problem in the regulation of gene expression.
Publishing Year
Date Published
2016-02-04
Journal Title
Physical Review E Statistical Nonlinear and Soft Matter Physics
Acknowledgement
We thank T. Gregor, A. Prochaintz, and others for helpful discussions. This work was supported in part by Grants No. PHY-1305525 and No. CCF-0939370 from the US National Science Foundation and by the W.M. Keck Foundation. A.M.W. acknowledges the support by European Research Council (ERC) Grant No. MCCIG PCIG10–GA- 2011–303561. G.T. and T.R.S. were supported by Austrian Science Fund (FWF) Grant No. P28844S.
Volume
93
Issue
2
Article Number
022404
IST-REx-ID

Cite this

Sokolowski TR, Walczak A, Bialek W, Tkacik G. Extending the dynamic range of transcription factor action by translational regulation. Physical Review E Statistical Nonlinear and Soft Matter Physics. 2016;93(2). doi:10.1103/PhysRevE.93.022404
Sokolowski, T. R., Walczak, A., Bialek, W., & Tkacik, G. (2016). Extending the dynamic range of transcription factor action by translational regulation. Physical Review E Statistical Nonlinear and Soft Matter Physics, 93(2). https://doi.org/10.1103/PhysRevE.93.022404
Sokolowski, Thomas R, Aleksandra Walczak, William Bialek, and Gasper Tkacik. “Extending the Dynamic Range of Transcription Factor Action by Translational Regulation.” Physical Review E Statistical Nonlinear and Soft Matter Physics 93, no. 2 (2016). https://doi.org/10.1103/PhysRevE.93.022404.
T. R. Sokolowski, A. Walczak, W. Bialek, and G. Tkacik, “Extending the dynamic range of transcription factor action by translational regulation,” Physical Review E Statistical Nonlinear and Soft Matter Physics, vol. 93, no. 2, 2016.
Sokolowski TR, Walczak A, Bialek W, Tkacik G. 2016. Extending the dynamic range of transcription factor action by translational regulation. Physical Review E Statistical Nonlinear and Soft Matter Physics. 93(2).
Sokolowski, Thomas R., et al. “Extending the Dynamic Range of Transcription Factor Action by Translational Regulation.” Physical Review E Statistical Nonlinear and Soft Matter Physics, vol. 93, no. 2, 022404, American Institute of Physics, 2016, doi:10.1103/PhysRevE.93.022404.

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