Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans

Authors: CHANG, WEN-JOU - Baylor College Of Medicine; BAKER, MARIA - Baylor College Of Medicine; LARITSKY, ELEONORA - Baylor College Of Medicine; GUNASEKARA, CHATHURA - Baylor College Of Medicine; MADURANGA, UDITHA - Baylor College Of Medicine; GALLIOU, JUSTINE - Cornell University; MCFADDEN, JOSEPH - Cornell University; WALTEMYER, JESSICA - Cornell University; BERGGREN-THOMAS, BRUCE - Cornell University; TATE, BRIANNA - Cornell University; ZHANG, HANXUE - Cornell University; Rosen, Benjamin - Ben; Van Tassell, Curtis - Curt; Liu, Ge - George; COARFA, CRISTIAN - Baylor College Of Medicine; YI, ATHENA - Cornell University; WATERLAND, ROBERT - Baylor College Of Medicine

Submitted to: Genome Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/13/2024
Publication Date: 7/15/2024
Citation: Chang, W., Baker, M., Laritsky, E., Gunasekara, C., Maduranga, U., Galliou, J.C., McFadden, J.W., Waltemyer, J.R., Berggren-Thomas, B., Tate, B.N., Zhang, H., Rosen, B.D., Van Tassell, C.P., Liu, G., Coarfa, C., Yi, A.R., Waterland, R.A. 2024. Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans. Genome Biology. 25(1). Article e185. https://doi.org/10.1186/s13059-024-03307-6.
DOI: https://doi.org/10.1186/s13059-024-03307-6

Interpretive Summary: Using our published results, we detected a special type of DNA methylation - CoRSIVs (the correlated regions of systemic interindividual epigenetic variation) in the cattle genome, which are similar to those in humans. These results fill our knowledge gaps and provide the foundation for future genetic improvement programs. Farmers, scientists, and policy planners who need to improve animal health and production based on genomic data will benefit from this study.

Technical Abstract: Background: We recently identified ~10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyzed publicly available whole-genome bisulfite sequencing (WGBS) data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle. Results: Focusing on genomic blocks with >= 5 CpGs and a systemic interindividual variation index of at least 20, our approach identifies 1,378 cattle CoRSIVs. Independent validation by bisulfite pyrosequencing yields a validation rate around 70%. Similar to human CoRSIVs, those in cattle are strongly associated with genetic variation and, remarkably, show long-range enrichments for LINE1 and LTR transposable elements and depletions in SINE elements and CpG islands. Lastly, we show that establishment of DNA methylation at cattle CoRSIVs is particularly sensitive to pre-pregnancy dietary methionine supplementation and assisted reproduction. Conclusions: Our data indicate that CoRSIVs exist in cattle, as in humans, suggesting these systemic epigenetic variants may be common to all mammals. To the extent that individual epigenetic variation at cattle CoRSIVs affects phenotypic outcomes, assessment of CoRSIV methylation at birth may become an important tool for optimizing agriculturally important traits. Moreover, optimized maternal nutrition or embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes by engineering CoRSIV methylation profiles.