Association of Aberrant DNA Methylation Level in the CD4 and JAK-STAT-Pathway-Related Genes with Mastitis Indicator Traits in Chinese Holstein Dairy Cattle

SIMPLE SUMMARY: Mastitis is the most common inflammatory disease of economic and animal welfare concern in dairy animals. The present study was designed to evaluate the gene expression and epigenetic modifications in cattle with mastitis and healthy cows. The CpG islands in the promoter regions of the JAK2 and the STAT5A revealed hypo-methylation levels and higher gene expression in cows with mastitis compared to the healthy control, and vice versa in those with the CD4 gene. DNA methylation was negatively correlated with gene expression in the JAK2 and CD4 genes. Findings of the current study showed that aberrant DNA methylation due to mastitis in the promoter region of the three genes under study could be used as potential epigenetic markers to predict the mastitis susceptibility in dairy cattle. ABSTRACT: The present study was designed to evaluate the gene expression and DNA methylation level in the promoter region of the CD4 and the JAK-STAT-pathway-related genes. A total of 24 samples were deployed in the gene expression and 118 samples were used in the DNA methylation study. Student’s t-tests were used to analyze the gene expression and DNA methylation. The evaluation of DNA methylation in promoter regions of JAK2 and STAT5A revealed hypo-methylation levels of CpG sites and higher gene expression in cows diagnosed with mastitis as compared to the healthy control, and vice versa in those with CD4. DNA methylation was negatively correlated with gene expression in JAK2, STAT5A, and CD4 genes. Six, two, and four active transcription factors were identified on the CpG sites in the promoter regions of JAK2, STAT5A, and CD4 genes, respectively. Regarding correlation analysis, the DNA methylation levels of CD4 showed significantly higher positive correlations with somatic cell counts (p < 0.05). Findings of the current study inferred that aberrant DNA methylation in the CpG sites at the 1 kb promoter region in JAK2, STAT5A, and CD4 genes due to mastitis in cows can be used as potential epigenetic markers to estimate bovine mastitis susceptibility in dairy cattle.