Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, 250100, China.
Sci Rep. 2017 Aug 29;7(1):9709. doi: 10.1038/s41598-017-10648-9.
DNA methylation changes play essential roles in regulating the activities of genes involved in immune responses. Understanding of variable DNA methylation linked to immune responses may contribute to identifying biologically promising epigenetic markers for pathogenesis of diseases. Here, we generated genome-wide DNA methylation and transcriptomic profiles of six pairs of polyinosinic-polycytidylic acid-treated pig peripheral blood mononuclear cell (PBMC) samples and corresponding controls using methylated DNA immunoprecipitation sequencing and RNA sequencing. Comparative methylome analyses identified 5,827 differentially methylated regions and 615 genes showing differential expression between the two groups. Integrative analyses revealed inverse associations between DNA methylation around transcriptional start site and gene expression levels. Furthermore, 70 differentially methylated and expressed genes were identified such as TNFRSF9, IDO1 and EBI3. Functional annotation revealed the enriched categories including positive regulation of immune system process and regulation of leukocyte activation. These findings demonstrated DNA methylation changes occurring in immune responses of PBMCs to poly I:C stimulation and a subset of genes potentially regulated by DNA methylation in the immune responses. The PBMC DNA methylome provides an epigenetic overview of this physiological system in response to viral infection, and we expect it to constitute a valuable resource for future epigenetic epidemiology studies in pigs.
DNA 甲基化变化在调节参与免疫反应的基因的活性方面起着重要作用。了解与免疫反应相关的可变 DNA 甲基化可能有助于确定疾病发病机制的有前途的生物学表观遗传标志物。在这里,我们使用甲基化 DNA 免疫沉淀测序和 RNA 测序生成了六对 polyinosinic-polycytidylic acid 处理的猪外周血单核细胞 (PBMC) 样本及其相应对照的全基因组 DNA 甲基化和转录组谱。比较甲基组分析鉴定了两组之间差异表达的 5827 个差异甲基化区域和 615 个基因。综合分析显示转录起始位点周围的 DNA 甲基化与基因表达水平之间存在反向关联。此外,还鉴定了 70 个差异甲基化和表达的基因,如 TNFRSF9、IDO1 和 EBI3。功能注释显示富含的类别包括免疫系统过程的正向调节和白细胞激活的调节。这些发现表明,在 PBMC 对 poly I:C 刺激的免疫反应中发生了 DNA 甲基化变化,并且有一组基因可能受到免疫反应中 DNA 甲基化的调节。PBMC 的 DNA 甲基组提供了对这种生理系统对病毒感染反应的表观遗传学概述,我们期望它成为未来猪的表观遗传学流行病学研究的有价值资源。