Integrative Methylome and Transcriptome Analysis of DNA Methylation and Sex-Biased Gene Expression in Northern Pike (Esox lucius)

Northern pike (Esox lucius) exhibits significant sexual growth dimorphism, yet the molecular basis of this sex-biased trait remains largely unexplored. In this study, we performed an integrative analysis of whole-genome DNA methylation (WGBS) and whole-transcriptome (RNA-seq) data from female and male gonadal tissues of E. lucius. Promoter methylation exhibited sexually dimorphic associations with gene expression: in females, promoter hypermethylation showed a positive correlation with elevated expression, whereas no such association was observed in males; gene body methylation was not correlated with expression in either sex. Integrative analysis identified a total of 508 methylation-associated differentially expressed genes (mDEGs), comprising 377 Hyper-Down (hypermethylated with downregulated expression) and 131 Hypo-Up (hypomethylated with upregulated expression) genes, from which 13 candidate genes were prioritized. Pathway enrichment analyses implicated TGF-β signaling, Wnt signaling, and progesterone-mediated oocyte maturation pathways, suggesting crosstalk between sex differentiation and metabolic regulation/signal transduction. Collectively, this study provides an exploratory perspective on the epigenetic landscape associated with sex differentiation in E. lucius. Our results reveal associations between promoter methylation and the expression of core sex-related genes, including dmrt1 (male-biased) and rspo1 (female-biased), which may be relevant to sex differentiation. The potential link between these epigenetic patterns and sexual growth dimorphism remains speculative and requires direct validation using growth-related phenotypic data and tissues.