Frequency-modulation of stochastic nuclear bursts facilitates gene expression coordination in yeast. A) In response to Ca2+, the Crz1 transcription factor localizes to the nucleus in stochastic bursts to activate target genes A and B. Target gene promoters have differential responses to activation by nuclear Crz1 due to variations in affinities or cooperativities (blue and red curves). B) For amplitude-modulation regulation (top panels), an increase in Ca2+ leads to a proportional increase in nuclear Crz1 levels (gray line), generating different ratios of expression of target gene A (blue dots, blue curve normalized to maximal expression) relative to target gene B (red dots, red curve normalized to maximal expression) for different Ca2+ concentrations. For frequency-modulation regulation (bottom panels), an increase in Ca2+ generates stochastic nuclear localization of Crz1 (gray line) that produces a fixed ratio of expression of target gene A (blue dots, blue curve normalized to maximal expression) relative to target gene B (red dots, red curve normalized to maximal expression) regardless of the Ca2+ concentration. Adapted from [3].