Integrated ATAC-seq and RNA-seq analysis reveals dynamic changes in chromatin accessibility and gene expression in...

Acrossocheilus fasciatus is an emerging economically important fish species in China, and Streptococcus agalactiae infection may pose a potential threat to its aquaculture. However, the epigenetic regulatory mechanisms underlying the response of A. fasciatus to S. agalactiae infection remain unclear. In this study, histological observation, RNA-seq, and ATAC-seq were integrated to systematically investigate tissue damage, transcriptomic changes, and chromatin accessibility dynamics in the brain of A. fasciatus after S. agalactiae infection. Histopathological analysis showed obvious lesions in the brain, intestine, and spleen of infected fish. ATAC-seq analysis revealed marked changes in chromatin accessibility in the brain, with 128,083, 163,535, and 142,031 accessible chromatin peaks identified at 0 h, 48 h, and 72 h, respectively. RNA-seq analysis identified 5406 and 7840 differentially expressed genes at 48 h and 72 h, respectively. These genes were mainly associated with biological processes such as immune response, response to stimulus, and signal transduction and were enriched in immune-related pathways, including cytokine-cytokine receptor interaction and TNF signaling pathway. Integrated ATAC-seq and RNA-seq analysis at 48 h identified 2193 overlapping genes showing both differential chromatin accessibility and differential expression. Among them, 513 genes exhibited increased chromatin accessibility accompanied by transcriptional upregulation and were mainly enriched in the NF-κB signaling pathway, T cell receptor signaling pathway, and TNF signaling pathway. Further analysis identified several candidate immune-related genes, including BCL6, CXCL12, SOCS3, CSF3, IL7R, and RHOH. Motif enrichment analysis suggested that transcription factors such as PHA-4, COUP-TFII, EAR2, Nkx6.1, and Isl1 may be involved in infection-associated transcriptional regulation. This study provides the first epigenetic insight into the brain response of A. fasciatus to S. agalactiae infection and offers a new framework for understanding host immune regulation in this species.