Approximating gene transcription dynamics using steady-state formulas.

Abstract

Understanding how genes in a single cell respond to dynamically changing signals has been a central question in stochastic gene transcription research. Recent studies have generated massive steady-state or snapshot mRNA distribution data of individual cells, and inferred a large spectrum of kinetic transcription parameters under varying conditions. However, there have been few algorithms to convert these static data into the temporal variation of kinetic rates. Real-time imaging has been developed to monitor stochastic transcription processes at the single-cell level, but the immense technicality has prevented its application to most endogenous loci in mammalian cells. In this article, we introduced a stochastic gene transcription model with variable kinetic rates induced by unstable cellular conditions. We approximated the transcription dynamics using easily obtained steady-state formulas in the model. We tested the approximation against experimental data in both prokaryotic and eukaryotic cells and further solidified the conditions that guarantee the robustness of the method. The method can be easily implemented to provide convenient tools for quantifying dynamic kinetics and mechanisms underlying the widespread static transcription data, and may shed a light on circumventing the limitation of current bursting data on transcriptional real-time imaging.