Histone Methyltransferase <i>MLL1</i> Mediates Oxidative Stress and Apoptosis upon Deoxynivalenol Exposure in the Intestinal Porcine Epithelial Cells
Dongfeng Shi,
Yiyi Shan,
Xiaoyang Zhu,
Haifei Wang,
Shenglong Wu,
Zhengchang Wu,
Wenbin Bao
Affiliations
Dongfeng Shi
Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
Yiyi Shan
Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
Xiaoyang Zhu
Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
Haifei Wang
Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
Shenglong Wu
Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
Zhengchang Wu
Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
Wenbin Bao
Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design of Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
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.
