DNA methylation differences of the BPI promoter among pig breeds and the regulation of gene expression

The bactericidal/permeability-increasing protein (BPI) exerts broad-spectrum bactericidal effects against Gram-negative bacteria and contributes to natural defenses. The expression patterns of BPI among different pig breeds and the underlying regulatory mechanisms remain elusive. In this study, we presented that the pig breeds of Yorkshire, Sutai and Meishan showed distinct BPI expression and promoter DNA methylation patterns. The promoter methylation level in Yorkshire pigs was significantly higher than that in Meishan pigs (P < 0.05), while the gene expression level displayed a reverse trend. Correlation analyses revealed a strong negative correlation between BPI promoter methylation and mRNA expression. Luciferase assay indicated that DNA methylation of BPI promoter can result in the reduction of BPI transcriptional activity in vitro. Furthermore, animals differing in E. coli F18 susceptibility showed that sensitive individuals had significantly higher promoter methylation and lower gene expression levels than those of resistant individuals (P < 0.05). Our study showed distinct BPI promoter methylation and gene expression patterns among different pig breeds, and provided evidence for the potential link between BPI promoter methylation, BPI expression and disease susceptibility. The findings bring us a step forward towards the understanding of regulatory mechanisms underlying BPI expression and provide fundamental information for further studies on elucidating the contribution of BPI to intestinal immunity.