  Cellular behaviors such as migration, division, and differentiation rely on
precise timing, and yet the molecular events that govern these behaviors are
highly stochastic. We investigate regulatory strategies that decrease the
timing noise of molecular events. Autoregulatory feedback increases noise. Yet,
we find that in the presence of regulation by a second species, autoregulatory
feedback decreases noise. To explain this finding, we develop a method to
calculate the optimal regulation function that minimizes the timing noise. The
method reveals that the combination of feedback and regulation minimizes noise
by maximizing the number of molecular events that must happen in sequence
before a threshold is crossed. We compute the optimal timing precision for all
two-node networks with regulation and feedback, derive a generic lower bound on
timing noise, and discuss our results in the context of neuroblast migration
during Caenorhabditis elegans development.
