Integrative epigenomic and transcriptomic profiling reveals organ-specific and coordinated cold stress responses in the brain and gill of Nile tilapia.

Cold stress is a major environmental challenge limiting the survival and productivity of tropical aquaculture species such as Nile tilapia (Oreochromis niloticus). The brain and gill represent two key organs that orchestrate systemic and environmental responses: the brain serves as the central thermosensory integrator and neuroendocrine control center, while the gill serves as the primary interface for respiration, ion regulation, and immune defense. However, the molecular mechanisms underlying their tissue-specific and potentially coordinated responses to cold remain unclear. Here, we applied integrative ATAC-seq and RNA-seq analyses to systematically investigate chromatin accessibility and gene expression dynamics in tilapia brain and gill tissues under cold stress. We identified thousands of differentially expressed genes and accessible regions, with significant correlations between transcriptional changes. Transcription factor footprinting revealed that Fra1 and Nrf act as key tissue-specific regulators, governing immune, apoptotic, and metabolic reprogramming in the brain and gill, respectively. Notably, the Fra1 module in the brain activated signaling pathways associated with stress response, neurodevelopment, and metabolic regulation which may influence peripheral responses by coordinating systemic physiological adjustments under cold stress, while Nrf-mediated regulation in the gill supported local homeostasis through redox and transport-related mechanisms. These findings highlight the hierarchical and organ-specific transcriptional control underlying cold adaptation in ectotherms. Our study provides the first chromatin accessibility atlas of cold-responsive regulatory networks across central and peripheral organs in fish, offering mechanistic insight and molecular targets for breeding cold-tolerant aquaculture strains.