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Reprogramming of histone methylation controls the differentiation of monocytes into macrophages
Author(s) -
Zheng QiFan,
Wang HuiMin,
Wang ZhanFeng,
Liu JinYang,
Zhang Qi,
Zhang Li,
Lu YuanHua,
You Han,
Jin GuangHui
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14060
Subject(s) - h3k4me3 , biology , chromatin immunoprecipitation , reprogramming , epigenetics , histone h3 , microbiology and biotechnology , histone , cellular differentiation , chromatin , regulation of gene expression , prc2 , gene expression , genetics , gene , promoter
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 ( TF s) 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 TF s, such as HOXA and FOXO genes, KLF 4, IRF 8 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 KLF 4 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.