Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada.
Department of Animal Science, Laval University, Quebec, QC, Canada.
BMC Biol. 2024 Mar 14;22(1):65. doi: 10.1186/s12915-024-01843-y.
DNA methylation has been documented to play vital roles in diseases and biological processes. In bovine, little is known about the regulatory roles of DNA methylation alterations on production and health traits, including mastitis.
Here, we employed whole-genome DNA methylation sequencing to profile the DNA methylation patterns of milk somatic cells from sixteen cows with naturally occurring Staphylococcus aureus (S. aureus) subclinical mastitis and ten healthy control cows. We observed abundant DNA methylation alterations, including 3,356,456 differentially methylated cytosines and 153,783 differential methylation haplotype blocks (dMHBs). The DNA methylation in regulatory regions, including promoters, first exons and first introns, showed global significant negative correlations with gene expression status. We identified 6435 dMHBs located in the regulatory regions of differentially expressed genes and significantly correlated with their corresponding genes, revealing their potential effects on transcriptional activities. Genes harboring DNA methylation alterations were significantly enriched in multiple immune- and disease-related pathways, suggesting the involvement of DNA methylation in regulating host responses to S. aureus subclinical mastitis. In addition, we found nine discriminant signatures (differentiates cows with S. aureus subclinical mastitis from healthy cows) representing the majority of the DNA methylation variations related to S. aureus subclinical mastitis. Validation of seven dMHBs in 200 cows indicated significant associations with mammary gland health (SCC and SCS) and milk production performance (milk yield).
In conclusion, our findings revealed abundant DNA methylation alterations in milk somatic cells that may be involved in regulating mammary gland defense against S. aureus infection. Particularly noteworthy is the identification of seven dMHBs showing significant associations with mammary gland health, underscoring their potential as promising epigenetic biomarkers. Overall, our findings on DNA methylation alterations offer novel insights into the regulatory mechanisms of bovine subclinical mastitis, providing further avenues for the development of effective control measures.
DNA 甲基化在疾病和生物过程中起着至关重要的作用。在牛中，关于 DNA 甲基化改变对生产和健康性状（包括乳腺炎）的调节作用知之甚少。
在这里，我们采用全基因组 DNA 甲基化测序技术，对 16 头患有金黄色葡萄球菌（S. aureus）亚临床乳腺炎的奶牛和 10 头健康对照奶牛的牛奶体细胞的 DNA 甲基化模式进行了分析。我们观察到丰富的 DNA 甲基化改变，包括 3,356,456 个差异甲基化胞嘧啶和 153,783 个差异甲基化单倍型块（dMHBs）。调控区域（包括启动子、第一外显子和第一内含子）的 DNA 甲基化与基因表达状态呈全局显著负相关。我们鉴定了 6435 个位于差异表达基因调控区域的 dMHBs，它们与相应基因显著相关，表明它们对转录活性有潜在影响。含有 DNA 甲基化改变的基因在多个免疫和疾病相关途径中显著富集，表明 DNA 甲基化参与调节宿主对金黄色葡萄球菌亚临床乳腺炎的反应。此外，我们发现了 9 个判别特征（区分患有金黄色葡萄球菌亚临床乳腺炎的奶牛和健康奶牛），代表了与金黄色葡萄球菌亚临床乳腺炎相关的大多数 DNA 甲基化变化。在 200 头奶牛中对 7 个 dMHBs 的验证表明，它们与乳腺健康（SCC 和 SCS）和产奶性能（产奶量）显著相关。
总之，我们的研究结果揭示了牛奶体细胞中丰富的 DNA 甲基化改变，这些改变可能参与调节乳腺对金黄色葡萄球菌感染的防御。值得注意的是，鉴定出的 7 个 dMHBs 与乳腺健康显著相关，这突出了它们作为有前途的表观遗传生物标志物的潜力。总的来说，我们关于 DNA 甲基化改变的研究结果为牛亚临床乳腺炎的调控机制提供了新的见解，为开发有效的控制措施提供了进一步的途径。
