1. Reprogramming of histone methylation controls the differentiation of monocytes into macrophages.
- Author
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Zheng QF, Wang HM, Wang ZF, Liu JY, Zhang Q, Zhang L, Lu YH, You H, and Jin GH
- Subjects
- Animals, Bone Marrow Cells cytology, Bone Marrow Cells enzymology, Bone Marrow Cells metabolism, Cell Differentiation, Cell Line, Tumor, Cells, Cultured, Chromatin Immunoprecipitation, Forkhead Transcription Factors, Homeodomain Proteins antagonists & inhibitors, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Humans, Kruppel-Like Factor 4, Lysine, Macrophages cytology, Methylation, Mice, Inbred C57BL, Monocytes cytology, Promoter Regions, Genetic, RNA Interference, Specific Pathogen-Free Organisms, Transcription Factors antagonists & inhibitors, Transcription Factors genetics, Epigenesis, Genetic, Gene Expression Regulation, Developmental, Histones metabolism, Macrophages metabolism, Monocytes metabolism, Protein Processing, Post-Translational, Transcription Factors metabolism
- 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., (© 2017 Federation of European Biochemical Societies.)
- Published
- 2017
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