Integrative ATAC-seq and RNA-seq reveal chromatin remodeling as a hub of immune, oxidative, and metabolic reprogramming under heat and hypoxia stress in Apostichopus japonicus.

Abstract

The sea cucumber Apostichopus japonicus holds significant economic importance in China's marine aquaculture. However, climate change-particularly extreme summer temperatures and hypoxia-has caused substantial economic losses in major production regions. These stressors impair the physiological, immunological, and survival ability of A. japonicus, with compounded high temperature and low oxygen stress exerting particularly severe effects. Using enzyme activity assays, RNA-seq, and ATAC-seq, we investigated how elevated temperature and hypoxia affect immune, antioxidant, and metabolic responses in A. japonicus (mean body weight 106 ± 15.3 g) under three conditions: optimal growth, low oxygen, and combined high temperature with low oxygen. Integrative analysis of transcriptomic and epigenomic data identified key co-expression modules and pathways associated with stress responses. Notably, the NF-κB signaling pathway emerged as a central regulator of immune and inflammatory responses under combined stress. Furthermore, genes involved in immune function (Orct2, bmp2), epigenetic regulation (DNMT), and protein homeostasis (ST8SIA1) exhibited coordinated changes in both chromatin accessibility and expression, revealing that chromatin remodeling underpins stress-induced transcriptional reprogramming. These findings demonstrate that A. japonicus responds to escalating environmental stress through hierarchical layers of signal transduction, epigenetic remodeling, and physiological output, with important implications for climate-adaptive aquaculture management.