PDF(Pubmed)
Abstract：
BACKGROUND: Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics.
RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways.
CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.
RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways.
CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.
摘要：
背景：现代家禽业中的脂肪肝出血性综合征（FLHS）主要由营养引起。尽管FLHS取得了令人鼓舞的进展，在表观遗传学方面，营养影响FLHS易感性的机制仍然缺乏。
结果：在这项研究中，我们通过染色质免疫沉淀测序（ChIP-seq）分析了组蛋白H3（H3K27me3）富集的三甲基化赖氨酸残基27的全基因组模式，并检查了其与健康和FLHS母鸡转录组的关联。研究结果表明，FLHS母鸡的H3K27me3水平在全基因组范围内增加。此外,发现H3K27me3占据整个基因和远处的基因间区域，可以起到类似消音器的调节元件的作用。对高甲基化峰中的转录因子（TF）基序的分析表明，有23种TF参与了肝脏代谢和发育的调节。转录组分析表明,差异表达基因(DEGs)在脂肪酸代谢中富集,氨基酸,和碳水化合物代谢。从PPI网络中鉴定出的hub基因是脂肪酸合成酶(FASN)。联合ChIP-seq和转录组分析显示，增加的H3K27me3和下调的基因在ECM-受体相互作用中有显著的富集，紧密连接,细胞粘附分子，附着者接合处，和TGF-β信号通路。
结论：总体而言，H3K27的三甲基化修饰已被证明在FLHS中具有显著的调节功能，介导与ECM-受体相互作用途径相关的关键基因的表达。这突出了H3K27me3的表观遗传机制，并为探索FLHS的核心调控目标和营养调控策略提供了见解。
结果：在这项研究中，我们通过染色质免疫沉淀测序（ChIP-seq）分析了组蛋白H3（H3K27me3）富集的三甲基化赖氨酸残基27的全基因组模式，并检查了其与健康和FLHS母鸡转录组的关联。研究结果表明，FLHS母鸡的H3K27me3水平在全基因组范围内增加。此外,发现H3K27me3占据整个基因和远处的基因间区域，可以起到类似消音器的调节元件的作用。对高甲基化峰中的转录因子（TF）基序的分析表明，有23种TF参与了肝脏代谢和发育的调节。转录组分析表明,差异表达基因(DEGs)在脂肪酸代谢中富集,氨基酸,和碳水化合物代谢。从PPI网络中鉴定出的hub基因是脂肪酸合成酶(FASN)。联合ChIP-seq和转录组分析显示，增加的H3K27me3和下调的基因在ECM-受体相互作用中有显著的富集，紧密连接,细胞粘附分子，附着者接合处，和TGF-β信号通路。
结论：总体而言，H3K27的三甲基化修饰已被证明在FLHS中具有显著的调节功能，介导与ECM-受体相互作用途径相关的关键基因的表达。这突出了H3K27me3的表观遗传机制，并为探索FLHS的核心调控目标和营养调控策略提供了见解。
