Elucidating the chromatin-driven transcription regulatory networks response to Streptococcus agalactiae infection under low temperature in Nile tilapia.

Low temperature impairs immune function in ectothermic vertebrates, but the underlying regulatory mechanisms remain unclear. Here, we show that hypothermia significantly decreases bacterial load and increases mortality in Nile tilapia (Oreochromis niloticus) following Streptococcus agalactiae infection. Integrative RNA-seq and ATAC-seq profiling of head kidney tissue revealed widespread suppression of immune gene expression under cold stress, including ifrd2, isg15, cxcr1, ccr2, ccr9a, and socs1b. Footprinting analysis of 259 transcription factor binding elements in accessible chromatin enabled the construction of a transcriptional regulatory network. Cold exposure reduced chromatin accessibility at immune-related transcription factors, including Irf1, Irf3, Irf4, and JunB, thereby dampening downstream gene activation. Irf1 emerged as a key regulator, coordinating the expression of interferon-responsive genes critical for antibacterial defense. Our findings uncover a chromatin-based mechanism of cold-induced immunosuppression in fish, highlighting Irf1-dependent regulatory control as a potential target for enhancing disease resistance under thermal stress.