Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
Frontier Science Center for Immunology and Metabolism, Hubei Key Laboratory of Cell Homeostasis, Hubei Key Laboratory of Developmentally Originated Disease, College of Life Sciences, Taikang Center for Life and Medical Sciences, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
J Gastroenterol Hepatol. 2023 Aug;38(8):1426-1437. doi: 10.1111/jgh.16252. Epub 2023 Jun 18.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The detailed epigenomic changes during fat accumulation in liver are not clear yet. Here, we performed ChIP-Seq analysis in the liver tissues of high-fat diet and regular chow diet mice and investigated the dynamic landscapes of H3K27ac and H3K9me3 marks on chromatin. We find that the activated typical enhancers marked with H3K27ac are enriched on lipid metabolic pathways in fat liver; however, super enhancers do not change much. The regions covered with H3K9me3 repressive mark seem to undergo great changes, and its peak number and intensity both decrease in fat liver. The enhancers located in lost H3K9me3 regions are enriched in lipid metabolism and inflammatory pathways; and motif analysis shows that they are potential targets for transcription factors involved in metabolic and inflammatory processes. Our study has revealed that H3K9me3 may play an important role during the pathogenesis of NAFLD through regulating the accessibility of enhancers.
非酒精性脂肪性肝病（NAFLD）是全球最常见的慢性肝病。脂肪在肝脏中积累时的详细表观基因组变化尚不清楚。在这里，我们对高脂肪饮食和常规饮食的小鼠的肝组织进行了 ChIP-Seq 分析，并研究了染色质上 H3K27ac 和 H3K9me3 标记的动态景观。我们发现，激活的典型增强子用 H3K27ac 标记，在脂肪肝的脂质代谢途径中富集；然而，超级增强子变化不大。被 H3K9me3 抑制标记覆盖的区域似乎发生了很大的变化，其峰数和强度在脂肪肝中都减少了。位于丢失的 H3K9me3 区域的增强子在脂质代谢和炎症途径中富集；并且 motif 分析表明，它们是涉及代谢和炎症过程的转录因子的潜在靶标。我们的研究表明，H3K9me3 通过调节增强子的可及性，可能在 NAFLD 的发病机制中发挥重要作用。
