Carrillo José A, He Yanghua, Luo Juan, Menendez Kimberly R, Tablante Nathaniel L, Zhao Keji, Paulson Joseph N, Li Bichun, Song Jiuzhou
Department of Animal and Avian Sciences, University of Maryland, College Park, Maryland, United States of America.
Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America.
PLoS One. 2015 Jun 24;10(6):e0100476. doi: 10.1371/journal.pone.0100476. eCollection 2015.
In this study we investigated the methylome of chickens immunized with Infectious laryngotracheitis (ILT) vaccine derived from chicken embryos. Methyl-CpG binding domain protein-enriched genome sequencing (MBD-Seq) method was employed in the detection of the 1,155 differentially methylated regions (DMRs) across the entire genome. After validation, we ascertained the genomic DMRs distribution and annotated them regarding genes, transcription start sites (TSS) and CpG islands. We found that global DNA methylation decreased in vaccinated birds, presenting 704 hypomethylated and 451 hypermethylated DMRs, respectively. Additionally, we performed an enrichment analysis detecting gene networks, in which cancer and RNA post-transcriptional modification appeared in the first place, followed by humoral immune response, immunological disease and inflammatory disease. The top four identified canonical pathways were EIF2 signaling, regulation of EIF4 and p70S6K signaling, axonal guidance signaling and mTOR signaling, providing new insight regarding the mechanisms of ILT etiology. Lastly, the association between DNA methylation and differentially expressed genes was examined, and detected negative correlation in seventeen of the eighteen genes.
在本研究中，我们调查了用源自鸡胚的传染性喉气管炎（ILT）疫苗免疫的鸡的甲基化组。采用甲基化CpG结合域蛋白富集基因组测序（MBD-Seq）方法检测全基因组中的1155个差异甲基化区域（DMR）。经过验证，我们确定了基因组DMR的分布，并对其进行了基因、转录起始位点（TSS）和CpG岛注释。我们发现，接种疫苗的鸡的整体DNA甲基化水平降低，分别出现了704个低甲基化DMR和451个高甲基化DMR。此外，我们进行了富集分析以检测基因网络，其中癌症和RNA转录后修饰位居首位，其次是体液免疫反应、免疫疾病和炎症性疾病。前四个确定的经典通路是EIF2信号通路、EIF4和p70S6K信号通路的调节、轴突导向信号通路和mTOR信号通路，为ILT病因机制提供了新的见解。最后，研究了DNA甲基化与差异表达基因之间的关联，在18个基因中的17个中检测到负相关。
