DNA Methylation of Pig FUT3 Promoter Alters mRNA Expression to Regulate E. coli F18 Susceptibility.

Zhengchang Wu,Hairui Fan,Jian Jin,Shenglong Wu,Wenbin Bao,Dongfeng Shi

doi:10.3390/genes12101586

Abstract

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.

Highlights

DNA methylation widely existing in mammals can regulate gene expression and maintain genetic stability with transcription and cell division
We identified 46 common differentially expressed genes (DEGs) between two pig breeds (Figure 1c,d). Among these DEGs, α-1,3-fucosyltransferase (FUT3) is involved in glycosphingolipid biosynthesis (KO pathway: ko00601) correlated with the generation of E. coli F18 receptor [19,20,21], which is probably considered as a novel target to combat E. coli F18 infection in piglets
Based on transcription factor prediction, we investigated several important transcription factors in FUT3 promoter CpG sites, which belongs to the methylation-dependent transcription factors and include hypoxia-inducible factor (HIF)-1α (HIF1A) [28], specificity protein 1 (SP1) [29,30], cAMP response elementbinding proteins (CREB) [31], upstream transcription factor (USF) [32], CCAAT/enhancerbinding protein β (C/EBPβ) [6]

Summary

Introduction

DNA methylation widely existing in mammals can regulate gene expression and maintain genetic stability with transcription and cell division. It has been reported that DNA methylation plays a crucial role in maintaining cell function, regulating individual development and disease [2,3,4]. DNA methylation is considered to be a significant research hotspot in the current field of pig genetics and breeding, relevant studies mainly focus on tissue-specific expression [5,6], cell apoptosis [7], variety differences [8], growth and development [9,10,11], immune response [12,13]. DNA methylation has been rarely reported in expression regulation of pig resistance to pathogenic microorganism infection

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Discussion

Conclusion