Epigenomic patterns in fish with divergent cortisol reactivity

Glucocorticoids (GCs), such as cortisol, bind to receptors in most tissues, triggering a stress response that enables individuals to adapt to stressors physiologically and behaviorally. GC signaling has been associated with plastic, stress-induced epigenetic modifications. However, the epigenetic profiles of individuals with divergent cortisol reactivity before and after a common challenge test have rarely been considered. Cortisol levels were measured in the blood plasma of 400 European seabass (Dicentrarchus labrax) to select 80 individuals exhibiting low- and high-responsiveness phenotypes. Weight, lysozyme activity, and plasma glucose and lactate levels were also measured. The methylome of blood samples from these individuals was investigated at 41,132 CpG positions before and after a 3-mo stress challenge test. We identified 273 differentially methylated cytosines, which mapped to 159 annotated differentially methylated genes (DMGs). We categorized differential methylation as "constitutive" or "induced," distinguishing between the two phenotypes in pre- and post-stress situations, respectively. Methylation observed at DMGs may also remain hypo- or hypermethylated in both contexts; however, seven of these showed a rewiring from hypo- to hypermethylation. Many DMGs are relevant to GC signaling, connecting to the non-genomic and genomic actions of cortisol. They can be considered as stress biomarkers monitored in the blood of this highly-prized species. Although our current study has limitations, we demonstrate the potential of a genome-wide epigenetic approach to studying endocrine divergence between stress-responsive fish phenotypes.NEW & NOTEWORTHY The association of DNA methylation with glucocorticoid signaling has attracted considerable interest. However, studies investigating genome-wide methylation differences in individuals with different cortisol responses before and after exposure to stress have been overlooked. Here, we demonstrate that the blood methylomes of fish with distinct cortisol responsiveness exhibit distinct pre-and post-stress methylation profiles, indicative of the cellular and organismal actions of cortisol possibly triggering the adaptive stress response of each phenotype in the face of stress.