Aramburu González, ÓscarGómez Pardo, María BelénRodríguez Villamayor, PaulaBlanco Hortas, AndrésLamas Fernández, JesúsBouza Fernández, María CarmenMartínez Portela, Paulino2025-10-132025-10-132025-07-15Oscar Aramburu, Belén Gómez-Pardo, Paula Rodríguez-Villamayor, Andrés Blanco-Hortas, Jesús Lamas, Pooran Dewari, Diego Perojil-Morata, Pierre Boudinot, Daniel J Macqueen, Carmen Bouza, Paulino Martínez, Multiomics uncovers the epigenomic and transcriptomic response to viral and bacterial stimulation in turbot, GigaScience, Volume 14, 2025, giaf077, https://doi.org/10.1093/gigascience/giaf0772047-217Xhttps://hdl.handle.net/10347/43070Background Uncovering the epigenomic regulation of immune response is essential for a comprehensive understanding of host defense mechanisms, though it remains poorly investigated in farmed fish. Results We report the first annotation of the response of turbot (Scophthalmus maximus) immune cells to viral (poly I:C) and bacterial (inactive Vibrio anguillarum) mimics, integrating RNA sequencing with assay for transposase-accessible chromatin (ATAC) sequencing (ATAC-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) (H3K4me3, H3K27ac, and H3K27me3) data from head kidney (in vivo) and primary leukocyte cultures (in vitro) 24 hours after stimulation. Among the 8,797 differentially expressed genes (DEGs), we observed enrichment of transcriptional activation pathways in response to Vibrio and immune pathways—including interferon-stimulated genes—for poly I:C. We identified notable differences in chromatin accessibility (20,617 in vitro, 59,892 in vivo) and H3K4me3-bound regions (11,454 in vitro, 10,275 in vivo) between stimulations and controls. Overlap of DEGs with promoters showing differential accessibility or histone mark binding revealed significant coupling of the transcriptome and chromatin state. DEGs with activation marks in their promoters were enriched for similar functions to the global DEG set but not always, suggesting key regulatory genes being in a poised state. Active promoters and putative enhancers were enriched in specific transcription factor binding motifs, many common to viral and bacterial responses. An in-depth analysis of chromatin state surrounding key DEGs encoding transcription factors was also performed to understand turbot immune response. Conclusions This multiomics investigation provides an improved understanding of the epigenomic basis of turbot immune response to mimics of viral and bacterial stimuli, offering novel functional genomic information that provides a valuable resource for exploring immune regulation in flatfish.eng© The Author(s) 2025. Published by Oxford University Press on behalf of GigaScience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/TurbotImmune responseEpigenomicsChromatin stateTranscription factorjournal article10.1093/gigascience/giaf077open access