背景:鹅,迁徙祖先的后代,经历了广泛的选择性育种,导致它们在肝脏中积累脂肪的显着能力,并表现出对大量能量摄入的高耐受性。因此,鹅为研究肥胖提供了一个很好的模型,代谢紊乱,和哺乳动物的肝脏疾病。尽管染色质在细胞核内的三维排列对基因表达和转录调控的影响已被广泛认可。鹅肝组织中脂肪沉积过程中染色质结构重组的确切功能仍需充分理解。
结果:在这项研究中,与没有明显炎症迹象的小鼠相比,食用高脂饮食(HFD)后,鹅的肝脏指数和甘油三酸酯(TG)含量变化更为明显。此外,我们对10个鹅肝组织进行了综合分析(5个HFD,5正常),包括生成染色质结构的高分辨率图,进行全基因组基因表达谱分析,并鉴定接受HFD的鹅和小鼠肝脏中的H3K27ac峰。我们的结果揭示了染色质结构的多尺度重组,包括A/B舱,拓扑关联域,以及启动子和增强子之间的相互作用。三维基因组结构的动态性,由HFD提示,在关键基因的转录调控中起着关键作用。此外,我们确定了调节染色质构象变化的基因,为响应过多的能量摄入,鹅的脂质沉积和肝脏脂肪变化的代谢适应过程。此外,我们进行了跨物种分析,比较了暴露于HFD的鹅和小鼠,与小鼠相比,揭示了鹅肝脏特有的独特特征。这些染色质构象的变化有助于阐明在过量能量摄入条件下观察到的鹅脂肪沉积和肝脏脂肪调节的特征。
结论:我们研究了鹅肝组织中HFD诱导的三维染色质结构和基因表达的动态修饰。我们进行了跨物种分析,比较了小鼠。我们的结果为鹅肝组织的染色质结构提供了重要的见解,为研究哺乳动物肝脏疾病提供了一个新的视角。
BACKGROUND: Goose, descendants of migratory ancestors, have undergone extensive selective breeding, resulting in their remarkable ability to accumulate fat in the liver and exhibit a high tolerance for significant energy intake. As a result, goose offers an excellent model for studying obesity, metabolic disorders, and liver diseases in mammals. Although the impact of the three-dimensional arrangement of chromatin within the cell nucleus on gene expression and transcriptional regulation is widely acknowledged, the precise functions of chromatin architecture reorganization during fat deposition in goose liver tissues still need to be fully comprehended.
RESULTS: In this study, geese exhibited more pronounced changes in the liver index and triglyceride (TG) content following the consumption of the high-fat diet (HFD) than mice without significant signs of inflammation. Additionally, we performed comprehensive analyses on 10 goose liver tissues (5 HFD, 5 normal), including generating high-resolution maps of chromatin architecture, conducting whole-genome gene expression profiling, and identifying H3K27ac peaks in the livers of geese and mice subjected to the HFD. Our results unveiled a multiscale restructuring of chromatin architecture, encompassing Compartment A/B, topologically associated domains, and interactions between promoters and enhancers. The dynamism of the three-dimensional genome architecture, prompted by the HFD, assumed a pivotal role in the transcriptional regulation of crucial genes. Furthermore, we identified genes that regulate chromatin conformation changes, contributing to the metabolic adaptation process of lipid deposition and hepatic fat changes in geese in response to excessive energy intake. Moreover, we conducted a cross-species analysis comparing geese and mice exposed to the HFD, revealing unique characteristics specific to the goose liver compared to a mouse. These chromatin conformation changes help elucidate the observed characteristics of fat deposition and hepatic fat regulation in geese under conditions of excessive energy intake.
CONCLUSIONS: We examined the dynamic modifications in three-dimensional chromatin architecture and gene expression induced by an HFD in goose liver tissues. We conducted a cross-species analysis comparing that of mice. Our results contribute significant insights into the chromatin architecture of goose liver tissues, offering a novel perspective for investigating mammal liver diseases.