Transcriptional bursting kinetics provide insights into the mechanisms governing Interferon-mediated transcriptional memory

Transcriptional memory has long been studied to understand the mechanisms underlying immunity development in response to external stressors. Certain genes display an enhanced transcriptional response upon re-exposure to specific stimuli. In this study, we focus on GBP5, a regulatory protein involved in immunity and inflammation, to investigate the kinetics of transcriptional bursts and their implications for long-term memory. To achieve this, we analyze single-cell snapshot images of nascent and mature mRNAs in HeLa cells at various time points during cytokine stimulation using single-molecule FISH imaging. We modeled the signaling pathway to reflect the overall trends observed in ensemble-averaged GBP5 transcript levels over longer time scales, coupling this with stochastic modeling to capture the bursty dynamics that typically occur over much shorter time scales. Rate kinetics were inferred using approximate Bayesian computation and sequential Monte Carlo sampling. By examining the spatiotemporal evolution of GBP5 transcripts and their associated kinetics, we shed some light on the underlying processes involved in transcriptional memory.