A computational model for cold entrainment of the ICE1-CBF-COR pathway in Arabidopsis

Higher plants have evolved a sophisticated mechanism to respond to cold stress, characterized by transiently pulsing the CBF3 transcriptional levels, while steadily increasing and maintaining a high homeostatic level of COR15A transcription. This response relies on a network of feedback loops involving Ca²⁺, calmodulin, kinases, and cold-regulated genes ( CBF3 and COR15A ). However, the dynamics and regulatory mechanisms of these cold-related genes remain incompletely understood. To address this, we developed a compact computational model simulating the ICE1-CBF-COR pathway in response to cold shock and periodic cold signals. The model accurately reproduced the dynamic cold-shock responses of the key gene variables in both wild-type and mutant plants, including the desensitization and resensitization characteristics of CBF3 and COR15A . The duration of cold tolerance under shock conditions was shown to depend on the basal parameters of the model. Furthermore, the model demonstrated robust circadian oscillations of CBF3 and COR15A under periodic cold signal entrainment, suggesting that diurnal temperature fluctuations might drive the circadian rhythms of these transcripts. • In the absence of aperiodic stimuli, reduced CaM levels and enhanced ZAT12-mediated negative feedback on CBF3 reproduced the desensitization of both CBF3 and COR15A . • Transient resensitization of CBF3 and COR15A to heat (under 24 hours) was eliminated following prolonged cold exposure (14 days). • The model predicted that cold tolerance would persist for approximately 10 days after cold shock exposure. • Periodic stimuli destabilized steady-state conditions, inducing sustained oscillations in the system. Notably, oscillation periodicity remained independent of parameter variations.