title: Extending the dynamic range of transcription factor action by translational regulation.
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.
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, A-3400 Klosterneuburg, Austria.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Sokolowski
authors.affiliation: CNRS-Laboratoire de Physique Théorique de l'École Normale Supérieure, 24 rue Lhomond, F-75005 Paris, France.
authors.forename: Aleksandra M
authors.initials: AM
authors.lastname: Walczak
authors.affiliation: Joseph Henry Laboratories of Physics, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: William
authors.initials: W
authors.lastname: Bialek
authors.affiliation: Institute of Science and Technology Austria, Am Campus 1, A-3400 Klosterneuburg, Austria.
authors.forename: Gašper
authors.initials: G
authors.lastname: Tkačik
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005786:Gene Expression Regulation; D008957:Models, Genetic; D014176:Protein Biosynthesis; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D014157:Transcription Factors