Abstract：
DNA methylation is an epigenetic modification that can alter gene expression, and the incidence can vary across developmental stages, inflammatory conditions, and sexes. The effects of viral maternal viral infection and sex on the DNA methylation patterns were studied in the hypothalamus of a pig model of immune activation during development. DNA methylation at single-base resolution in regions of high CpG density was measured on 24 individual hypothalamus samples using reduced representation bisulfite sequencing. Differential over- and under-methylated sites were identified and annotated to proximal genes and corresponding biological processes. A total of 120 sites were differentially methylated (FDR-adjusted p-value < 0.05) between maternal infection or sex groups. Among the 66 sites differentially methylated between groups exposed to inflammatory signals and control, most sites were over-methylated in the challenged group and included sites in the promoter regions of genes SIRT3 and NRBP1. Among the 54 differentially methylated sites between females and males, most sites were over-methylated in females and included sites in the promoter region of genes TNC and EIF4G1. The analysis of the genes proximal to the differentially methylated sites suggested that biological processes potentially impacted include immune response, neuron migration and ensheathment, peptide signaling, adaptive thermogenesis, and tissue development. These results suggest that translational studies should consider that the prolonged effect of maternal infection during gestation may be enacted through epigenetic regulatory mechanisms that may differ between sexes.
摘要：
DNA甲基化是一种表观遗传修饰，可以改变基因表达，发病率可能因发育阶段而异，炎症条件，和性别。在发育过程中免疫激活的猪模型的下丘脑中研究了病毒母体病毒感染和性别对DNA甲基化模式的影响。使用减少的代表性亚硫酸氢盐测序在24个单独的下丘脑样品上测量高CpG密度区域中的单碱基分辨率的DNA甲基化。鉴定了差异的甲基化过度和甲基化不足位点，并将其注释为近端基因和相应的生物学过程。在母体感染或性别组之间，共有120个位点差异甲基化（FDR调整的p值<0.05）。在暴露于炎症信号和对照组之间的66个差异甲基化位点中，在攻击组中,大多数位点过度甲基化,并包括SIRT3和NRBP1基因启动子区的位点.在女性和男性之间的54个差异甲基化位点中，大多数位点在女性中过度甲基化，并且包括基因TNC和EIF4G1的启动子区域中的位点。对差异甲基化位点附近的基因的分析表明，可能受到影响的生物过程包括免疫反应，神经元迁移和鞘膜，肽信号，适应性产热，和组织发育。这些结果表明，翻译研究应考虑到妊娠期间母体感染的长期影响可能是通过性别之间可能不同的表观遗传调节机制来实现的。
