Epigenetic association study uncovered H3K27 acetylation enhancers and dysregulated genes in high-fat-diet-induced nonalcoholic fatty liver disease in rats.
Jinhu MaDandan YouShuwen ChenNana FangXinrui YiYi WangXuejin LuXinyu LiMeizi ZhuMin XueYunshu TangXiaohui WeiJianzhen HuangYaling ZhuPublished in: Epigenomics (2023)
Aim: 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. Materials & methods: H3K27ac chromatin immunoprecipitation and high-throughput RNA sequencing to construct regulatory profiles and transcriptome of liver from NAFLD rat model induced by HFD. De novo 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. Results: A total of 1831 differential H3K27ac peaks were identified significantly correlating with transcription factors and target genes ( CYP8B1 , PLA2G12B , SLC27A5 , CYP7A1 and APOC3 ) involved in lipid and energy homeostasis. Conclusion: Altered acetylation induced by HFD leads to the dysregulation of gene expression, further elucidating the epigenetic mechanism in the etiology of NAFLD.
Keyphrases
- high fat diet
- gene expression
- genome wide
- transcription factor
- dna methylation
- insulin resistance
- genome wide identification
- adipose tissue
- single cell
- high fat diet induced
- real time pcr
- high throughput
- protein protein
- bioinformatics analysis
- dna damage
- small molecule
- rna seq
- skeletal muscle
- genome wide analysis
- high resolution
- oxidative stress
- south africa