Diet-induced obesity dysregulates rapid epigenetic response to hypoxia in macrophages (RNA-Seq)

Macrophages play important roles in tissue homeostasis and tissue healing process. The response to hypoxic environment is a trigger to induce key signaling pathways in macrophages. Functions of macrophages are dysregulated in metabolic diseases such as diabetes and obesity resulting in poor tissue healing. Epigenetic status including histone modification in macrophages is regulated by hypoxia. However, whether and how obesity influences histone modification under hypoxia is unknown. Using chromatin immunoprecipitation-sequencing (ChIP-seq), RNA-seq on mouse bone marrow-derived macrophages, we sought to determine whether hypoxia alters histone 3-lysine 4 trimethylation (H3K4me3) and gene expression profile in macrophages and how obesity influences H3K4me3 enrichment on the genome in hypoxia-dependent and -independent manner. Overall design: Gene expression profile analysis of RNA-seq data for bone marrow-derived macrophages (BMDMs) cultured from C57B6/J mice fed a high-fat diet or a normal-fat diet.

巨噬细胞（Macrophages）在组织稳态维持与组织修复过程中发挥关键作用。低氧应答是激活巨噬细胞关键信号通路的触发因素。在糖尿病、肥胖等代谢性疾病中，巨噬细胞功能失调会导致组织修复能力受损。巨噬细胞内包括组蛋白修饰（histone modification）在内的表观遗传状态受低氧环境调控。然而，肥胖是否以及如何在低氧环境下影响组蛋白修饰，目前尚不明确。本研究通过对小鼠骨髓来源巨噬细胞（bone marrow-derived macrophages, BMDMs）开展染色质免疫共沉淀测序（chromatin immunoprecipitation-sequencing, ChIP-seq）与RNA测序（RNA-seq），旨在明确低氧是否会改变巨噬细胞内的组蛋白H3赖氨酸4三甲基化（histone 3-lysine 4 trimethylation, H3K4me3）水平与基因表达谱，以及肥胖如何以低氧依赖或非依赖的方式，影响基因组上H3K4me3的富集情况。实验设计：对取自喂食高脂饲料（high-fat diet）或普通饲料（normal-fat diet）的C57B6/J小鼠的骨髓来源巨噬细胞（BMDMs）的RNA-seq数据开展基因表达谱分析。