Different effects of fast and slow input fluctuations on output in gene regulation

An important task in the post-gene era is to understand the role of stochasticity in gene regulation. Here, we analyze a cascade model of stochastic gene expression, where the upstream gene stochastically generates proteins that regulate, as transcription factors, stochastic synthesis of the downstream output. We find that in contrast to fast input fluctuations that do not change the behavior of the downstream system qualitatively, slow input fluctuations can induce different modes of the distribution of downstream output and even stochastic focusing or defocusing of the downstream output level, although the regulatory protein follows the same distribution in both cases. This finding is counterintuitive but can have broad biological implications, e.g., slow input rather than fast fluctuations may both increase the survival probability of cells and enhance the sensitivity of intracellular regulation. In addition, we find that input fluctuations can minimize the output noise.