title: Reprogramming of histone methylation controls the differentiation of monocytes into macrophages.
abstract: 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.
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, China.|State Key Laboratory of Cellular Stress Biology, Xiamen University, China.|Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma, Xiamen University, China.
authors.forename: Qi-Fan
authors.initials: QF
authors.lastname: Zheng
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, China.
authors.forename: Zhan-Feng
authors.initials: ZF
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, China.
authors.forename: Jin-Yang
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Xiamen University, China.
authors.forename: Han
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Basic Medical Sciences, Medical College, Xiamen University, China.|State Key Laboratory of Cellular Stress Biology, Xiamen University, China.|Fujian Provincial Key Laboratory of chronic liver disease and hepatocellular carcinoma, Xiamen University, China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Jin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D044127:Epigenesis, Genetic; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008239:Lysine; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008745:Methylation; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D013047:Specific Pathogen-Free Organisms; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D006657:Histones; D018398:Homeodomain Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors; D008239:Lysine
keywords: PcG; TrxG; differentiation; monocyte; phagocyte