A theoretical study on activation of transcription factor modulated by intracellular Ca2+ oscillations

This work presents both deterministic and stochastic models of genetic expression modulated by intracellular calcium (Ca2+) oscillations, based on macroscopic differential equations and chemical Langevin equations, respectively. In deterministic case, the oscillations of intracellular Ca2+ decrease the effective Ca2+ threshold for the activation of transcriptional activator (TF-A). The average activation of TF-A increases with the increase of the average amplitude of intracellular Ca2+ oscillations, but decreases with the increase of the period of intracellular Ca2+ oscillations, which are qualitatively consistent with the experimental results on the gene expression in lymphocytes. In stochastic case, it is found that a large internal fluctuation of the biochemical reaction can enhance gene expression efficiency specifically at a low level of external stimulations or at a small rate of TF-A dimer phosphorylation activated by Ca2+, which reduces the threshold of the average intracellular Ca2+ concentration for gene expression.