Epigenetic landscape of hormone-independent sexual dimorphism and characterization of canine XIST

Sexual dimorphism in dogs (Canis lupus familiaris) manifests through pronounced differences in morphology, physiology, and disease susceptibility. Despite early neutering, sex-specific differences in dogs persist, highlighting the need to investigate factors beyond sex hormones that contribute to these characteristics. This study investigated sex-specific epigenetic modifications in neutered dogs. The results indicated hormone-independent, sex-related differentially methylated genes related to oncogenic signaling and neuronal pathways. The differences in methylation status between the sexes were significantly associated with alterations in gene expression, indicating that methylation plays a regulatory role in gene transcription. Identification of canine XIST, previously annotated as LOC102156855, suggested a conserved mechanism of X-chromosome inactivation across species and a sex-specific epigenetic imprint on the genome, which is maintained independent of sex hormones. These findings enrich the understanding of sex-specific biology in dogs and highlight the intricate interplay between epigenetic modification and gene expression in determining sex-specific phenotypes and disease susceptibilities.