Ma Jinhu, You Dandan, Chen Shuwen, Fang Nana, Yi Xinrui, Wang Yi, Lu Xuejin, Li Xinyu, Zhu Meizi, Xue Min, Tang Yunshu, Wei Xiaohui, Huang Jianzhen, Zhu Yaling
Department of Pathophysiology, Anhui Medical University, Hefei, 230032, China.
College of Animal Science & Technology, Jiangxi Agricultural University, Nanchang, 330045, China.
Epigenomics. 2022 Dec;14(23):1523-1540. doi: 10.2217/epi-2022-0362. Epub 2023 Feb 22.
To evaluate the regulatory landscape underlying the active enhancer marked by H3K27ac in high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats. H3K27ac chromatin immunoprecipitation and high-throughput RNA sequencing to construct regulatory profiles and transcriptome of liver from NAFLD rat model induced by HFD. motif analysis for differential H3K27ac peaks. Functional enrichment, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction network were examined for differential peak-genes. The mechanism was further verified by western blot, chromatin immunoprecipitation-quantitative PCR and real-time PCR. A total of 1831 differential H3K27ac peaks were identified significantly correlating with transcription factors and target genes (, , , and ) involved in lipid and energy homeostasis. Altered acetylation induced by HFD leads to the dysregulation of gene expression, further elucidating the epigenetic mechanism in the etiology of NAFLD.
评估高脂饮食（HFD）诱导的大鼠非酒精性脂肪性肝病（NAFLD）中以H3K27ac标记的活性增强子的调控格局。采用H3K27ac染色质免疫沉淀和高通量RNA测序技术构建HFD诱导的NAFLD大鼠模型肝脏的调控图谱和转录组。对差异H3K27ac峰进行基序分析。对差异峰基因进行功能富集、京都基因与基因组百科全书通路和蛋白质-蛋白质相互作用网络分析。通过蛋白质印迹、染色质免疫沉淀-定量PCR和实时PCR进一步验证其机制。共鉴定出1831个差异H3K27ac峰，它们与参与脂质和能量稳态的转录因子和靶基因（、、、和）显著相关。HFD诱导的乙酰化改变导致基因表达失调，进一步阐明了NAFLD病因中的表观遗传机制。
