Reprogramming of histone methylation controls the differentiation of monocytes into macrophages
Reprogramming of histone methylation controls the differentiation of monocytes into macrophages
复制标题
组蛋白甲基化重编程控制单核细胞分化为巨噬细胞
DOI：
10.1111/febs.14060
复制
发表时间：
2017
期刊：
影响因子：
5.4
通讯作者：
Jin Guang-Hui
中科院分区：
文献类型：
--
作者：
Zheng Qi-Fan;Wang Hui-Min;Wang Zhan-Feng;Liu Jin-Yang;Zhang Qi;Zhang Li;Lu Yuan-Hua;You Han;Jin Guang-Hui
单核吞噬细胞系统（MPS）的亚群异质性由定义的转录网络和程序控制;然而，在单核细胞向吞噬细胞（MP）分化的过程中，控制转录因子（TF）广泛、协调表达的程序的动态建立在很大程度上仍未探索。通过使用染色质免疫沉淀试验，我们显示了组蛋白H3赖氨酸4（H3 K4 me 3）的广泛三甲基化以及组蛋白H3赖氨酸27（H3 K27 me 3）在MP分化相关TF（如HOXA和FOXO基因，KLF 4，IRF 8等）启动子处的广泛足迹。HOXA基因的快速阻遏与MP分化程序密切相关。H3 K4 me 3在轻度和终末分化期参与调节HOXA基因，而H3 K27 me 3在吞噬维持期维持HOXA基因的低水平表达。此外，H3 K27 me 3的重编程在MP分化期间KLF 4和FOXO基因的上调中起主要作用。重要的是，H3 K4 me 3和/或H3 K27 me 3的药理学抑制显着促进THP-1和K562细胞的分化程序。总之，这些发现阐明了表观遗传记忆的动态建立的关键机制，这是维持MP分化阻断的核心。
Subset heterogeneity of the mononuclear phagocyte system (MPS) is controlled by defined transcriptional networks and programs; however, the dynamic establishment of programs that control broad, orchestrated expression of transcription factors (TFs) during the progression of monocyte‐into‐phagocyte (MP) differentiation remains largely unexplored. By using chromatin immunoprecipitation assays, we show the extensive trimethylation of histone H3 lysine 4 (H3K4me3) as well as histone H3 lysine 27 (H3K27me3) occupancy with broad footprints at the promoters of MP differentiation‐related TFs, such as HOXA and FOXO genes, KLF4, IRF8 and others. The rapid repression of HOXA genes was closely associated with the MP differentiation program. H3K4me3 participates in regulating HOXA genes at mild and terminal differentiation periods, while H3K27me3 maintains low‐level expression of HOXA genes at phagocytic maintenance periods. Furthermore, the reprogramming of H3K27me3 plays a major role in the up‐regulation of KLF4 and FOXO genes during MP differentiation. Importantly, the pharmacological inhibition of H3K4me3 and/or H3K27me3 strikingly promotes the differentiation programs of THP‐1 and K562 cells. Together, these findings elucidate mechanisms crucial to the dynamic establishment of epigenetic memory, which is central to the maintenance of the MP differentiation blockade.