Tan Xiaodong, Liu Ranran, Zhang Yonghong, Wang Xicai, Wang Jie, Wang Hailong, Zhao Guiping, Zheng Maiqing, Wen Jie
State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
College of Animal Science, Jilin University, Changchun, 130062, China.
BMC Genomics. 2021 Jan 6;22(1):8. doi: 10.1186/s12864-020-07305-3.
DNA methylation, a biochemical modification of cytosine, has an important role in lipid metabolism. Fatty liver hemorrhagic syndrome (FLHS) is a serious disease and is tightly linked to lipid homeostasis. Herein, we compared the methylome and transcriptome of chickens with and without FLHS.
We found genome-wide dysregulated DNA methylation pattern in which regions up- and down-stream of gene body were hypo-methylated in chickens with FLHS. A total of 4155 differentially methylated genes and 1389 differentially expressed genes were identified. Genes were focused when a negative relationship between mRNA expression and DNA methylation in promoter and gene body were detected. Based on pathway enrichment analysis, we found expression of genes related to lipogenesis and oxygenolysis (e.g., PPAR signaling pathway, fatty acid biosynthesis, and fatty acid elongation) to be up-regulated with associated down-regulated DNA methylation. In contrast, genes related to cellular junction and communication pathways (e.g., vascular smooth muscle contraction, phosphatidylinositol signaling system, and gap junction) were inhibited and with associated up-regulation of DNA methylation.
In the current study, we provide a genome-wide scale landscape of DNA methylation and gene expression. The hepatic hypo-methylation feature has been identified with FLHS chickens. By integrated analysis, the results strongly suggest that increased lipid accumulation and hepatocyte rupture are central pathways that are regulated by DNA methylation in chickens with FLHS.
DNA甲基化是胞嘧啶的一种生化修饰，在脂质代谢中起重要作用。脂肪肝出血综合征（FLHS）是一种严重疾病，与脂质稳态密切相关。在此，我们比较了患有和未患有FLHS的鸡的甲基化组和转录组。
我们发现全基因组DNA甲基化模式失调，在患有FLHS的鸡中，基因体上下游区域甲基化不足。共鉴定出4155个差异甲基化基因和1389个差异表达基因。当检测到启动子和基因体中mRNA表达与DNA甲基化呈负相关时，对基因进行了聚焦分析。基于通路富集分析，我们发现与脂肪生成和氧解相关的基因（如PPAR信号通路、脂肪酸生物合成和脂肪酸延长）表达上调，同时DNA甲基化下调。相反，与细胞连接和通讯通路相关的基因（如血管平滑肌收缩、磷脂酰肌醇信号系统和缝隙连接）受到抑制，同时DNA甲基化上调。
在本研究中，我们提供了全基因组范围的DNA甲基化和基因表达图谱。已确定患有FLHS的鸡具有肝脏甲基化不足的特征。通过综合分析，结果强烈表明脂质积累增加和肝细胞破裂是FLHS鸡中受DNA甲基化调控的核心途径。
