Integrated analysis of methylation profiles and transcriptome of Marek?s disease virus-infected chicken spleens reveal hypomethylation of CD4 and HMGB1 genes might promote Marek?s disease tumorigenesis

文献类型： 外文期刊

第一作者： Yuan, Yiming

作者： Yuan, Yiming;Zheng, Gang;You, Zhen;Wang, Lulu;Wang, Ziyi;Sun, Congjiao;Yang, Ning;Lian, Ling;Liu, Changjun;Li, Xianyao;Zhao, Peng;Wang, Yongqiang

作者机构：

关键词： chicken; Marek?s disease; DNA methylation

期刊名称：POULTRY SCIENCE （ 影响因子：4.4； 五年影响因子：4.4 ）

ISSN： 0032-5791

年卷期： 2023 年 102 卷 6 期

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收录情况： SCI

摘要： Marek's disease (MD) is a lymphoproli-ferative neoplastic disease caused by Marek's disease virus (MDV). Previous studies have showed that DNA methylation was involved in MD development, but sys-tematic studies are still lacking. Herein, we performed whole genome bisulfite sequencing (WGBS) and RNA-seq in MDV-infected tumorous spleens (IN), non -infected spleens (NoIN), and survivor (SUR) spleens of chickens to identify the genes playing important roles in MD tumor transformation. We generated the first genome-wide DNA methylation profile of MDV-infected, noninfected, and survivor chickens. Combined the WGBS and RNA-Seq, we found that the expression of 25% differential expression genes (DEGs) were sig-nificantly correlated with methylation of CpG sites in their gene bodies or promoters. Further, we focused on the DEGs with differentially methylated regions (DMRs) on genes' body and promoter, and it showed the expression of 60% DEGs were significantly corre-lated with methylation of CpG sites in DMRs. Finally, we identified 8 genes, including CD4, CTLA4, DTL, HMGB1, LGMN, NUP210, RAD52, and ZAP70, and their expression was negatively correlated with methyl-ation of DMRs in their promoters in both IN vs. NoIN and IN vs. SUR. These 8 genes showed specifically high expression in IN groups and clustered in module tur-quoise analyzed by WGCNA. Out of 8 genes, CD4 and HMGB1 were drop in QTLs associated with MD resis-tance. Thus, we overexpressed the 2 genes to simulate their high expression in the IN group and found they significantly promoted MDCC-MSB-1 cell proliferation, which revealed they might play promoting roles in MD tumorigenesis in IN due to their high expression induced by hypomethylation.

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