Post-weaning diarrhea (PWD) is frequently associated with E. coli F18 infections in piglets. However, the underlying molecular mechanism concerning the resistance of E. coli F18 in local weaned piglets in China is not clearly understood. In the present study, by a comparative analysis of the transcriptome, a-1,3-fucosyltransferase (FUT3) was evaluated as a key candidate correlated with resistance to E. coli F18 in Sutai and Meishan piglets. Functional analysis demonstrated that FUT3 acts as a key positive regulator of E. coli F18 susceptibility in newly food accustomed piglets. However, the core promoter of FUT3 was present at −500–(−206) bp (chr.2: g.73171117–g.73171616), comprising of 9 methylated CpG sites. Among these, the methylation levels of the two CpG sites (mC-3, mC-5) located in HIF1A and Sp1 transcription factor (TF) considerably associated with mRNA expression of FUT3 (p < 0.05). Our findings indicated that the methylation of mC-3 and mC-5 sites has certain inhibitory effect on FUT3 expression and promotes the resistance of E. coli F18 in piglets. The underlined study may explore FUT3 as a new candidate target in E. coli F18 infection in Chinese local weaned piglets.

Deoxynivalenol (DON), as a secondary metabolite of fungi, is continually detected in livestock feed and has a high risk to animals and humans. Moreover, pigs are very sensitive to DON. Recently, the role of histone modification has drawn people’s attention; however, few studies have elucidated how histone modification participates in the cytotoxicity or genotoxicity induced by mycotoxins. In this study, we used intestinal porcine epithelial cells (IPEC-J2 cells) as a model to DON exposure in vitro. Mixed lineage leukemia 1 (MLL1) regulates gene expression by exerting the role of methyltransferase. Our studies demonstrated that H3K4me3 enrichment was enhanced and MLL1 was highly upregulated upon 1 μg/mL DON exposure in IPEC-J2 cells. We found that the silencing of MLL1 resulted in increasing the apoptosis rate, arresting the cell cycle, and activating the mitogen-activated protein kinases (MAPKs) pathway. An RNA-sequencing analysis proved that differentially expressed genes (DEGs) were enriched in the cell cycle, apoptosis, and tumor necrosis factor (TNF) signaling pathway between the knockdown of MLL1 and negative control groups, which were associated with cytotoxicity induced by DON. In summary, these current results might provide new insight into how MLL1 regulates cytotoxic effects induced by DON via an epigenetic mechanism.