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

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

Poultry Science (Jun 2023)

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

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

Affiliations

Yiming Yuan: National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Gang Zheng: National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Zhen You: National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Lulu Wang: National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Ziyi Wang: National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Congjiao Sun: National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Changjun Liu: Division of Avian Infectious Diseases, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Harbin 150001, China
Xianyao Li: College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Tai'an 271018, China
Peng Zhao: College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China
Yongqiang Wang: College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
Ning Yang: National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
Ling Lian: National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; Corresponding author:

Journal volume & issue: Vol. 102, no. 6
p. 102594

Abstract

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ABSTRACT: Marek's disease (MD) is a lymphoproliferative neoplastic disease caused by Marek's disease virus (MDV). Previous studies have showed that DNA methylation was involved in MD development, but systematic studies are still lacking. Herein, we performed whole genome bisulfite sequencing (WGBS) and RNA-seq in MDV-infected tumorous spleens (IN), noninfected 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 significantly 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 correlated 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 methylation 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 turquoise analyzed by WGCNA. Out of 8 genes, CD4 and HMGB1 were drop in QTLs associated with MD resistance. 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.

Published in Poultry Science

ISSN: 0032-5791 (Print); 1525-3171 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Agriculture: Animal culture
Website: https://www.journals.elsevier.com/poultry-science

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