Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/29/2025
Publication Date: 5/1/2025
Citation: Hu, Z., Boschiero, C., Neupane, M., Bhowmik, N., Yang, L., Kilian, L., DeJarnette, M., Sargolzaei, M., Harstine, B., Li, C., Tuo, W., Baldwin, R.L., Van Tassell, C.P., Sattler, C.G., Liu, G. 2025. Exploring tissue- and sex-specific DNA methylation in cattle using a pan-mammalian infinium array. International Journal of Molecular Sciences. 26(9): 4284. https://doi.org/10.3390/ijms26094284.
DOI: https://doi.org/10.3390/ijms26094284

Interpretive Summary: Tradition breeding efforts to introduce desirable production traits in dairy cattle took decades to achieve the desired production outcome, which at times also increase undesirable traits. The ability to assess an organism’s entire genetic material (genome) has allowed incorporation of genetic assisted approaches in breeding regimens, allowing more rapidly select for production traits of economic value. However, there is a need to understand how genes controlling traits are regulated in the cell and to develop approaches to artificially influence those mechanisms. One such cell mechanism, DNA methylation, can turn on or off the generation of gene products important for biological functions during organ development and differentiation of the sexes. We studied how DNA methylation changes between different tissues and between male and female dairy cattle. From the resultant data, significant variability in DNA methylation patterns were found across tissues and sexes, which regulate animal growth and reproduction. These results help dairy cattle scientists develop better approaches to incorporate our understanding of genetics into future breeding programs for the dairy farmers and industry to improve both animal productivity and health.

Technical Abstract: DNA methylation plays a crucial role in gene expression regulation and tissue differentiation in livestock. However, genome-wide methylation patterns among tissues remain underexplored in cattle, one of the world's most important farm animals. This study investigates tissue-specific DNA methylation and sex-based differences in cattle using CpG site methylation data generated from the Infinium DNA Methylation array across seven tissues. Our analysis revealed significant tissue-specific methylation differences, with reproductive tissues, such as sperm, exhibiting distinct profiles compared to somatic tissues like hair and blood. Principal component analysis (PCA) highlighted tissue differentiation as the primary driver of methylation variability. We also identified 222 CpG sites with significant sex-based methylation differences, particularly on the X chromosome, suggesting potential epigenetic regulation of sex-specific traits. Gene ontology (GO) enrichment analysis indicated that these methylation patterns may influence biological processes such as epithelial cell proliferation and blood vessel remodeling. Overall, this study provides important insights into tissue-specific and sex-based epigenetic regulation in cattle, with implications for improving livestock breeding strategies through integrating epigenetic data.