Extending the dynamic range of transcription factor action by translational regulation Journal Article

Author(s): Sokolowski, Thomas R; Walczak, Aleksandra M; Bialek, William; Tkačik, Gašper
Article Title: Extending the dynamic range of transcription factor action by translational regulation
Affiliation IST Austria
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.
Journal Title: Physical Review E Statistical Nonlinear and Soft Matter Physics
Volume: 93
Issue 2
ISSN: 1539-3755
Publisher: American Institute of Physics  
Date Published: 2016-02-04
Start Page: Article number: 022404
DOI: 10.1103/PhysRevE.93.022404
Notes: 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.
Open access: yes (repository)