  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 transcription factors. Intuitively, each mRNA molecule acts
as an independent sensor of the TF concentration, and averaging over these
multiple sensors reduces the noise. We analyze information flow through this
new 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.
