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Reprogramming of histone methylation controls the differentiation of monocytes into macrophages.
- Source :
-
The FEBS journal [FEBS J] 2017 May; Vol. 284 (9), pp. 1309-1323. Date of Electronic Publication: 2017 Apr 04. - Publication Year :
- 2017
-
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.<br /> (© 2017 Federation of European Biochemical Societies.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1742-4658
- Volume :
- 284
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The FEBS journal
- Publication Type :
- Academic Journal
- Accession number :
- 28304152
- Full Text :
- https://doi.org/10.1111/febs.14060