Table 1.
Histone methyltransferases, histone demethylases, target histone sites, and their roles in the occurrence and development of osteoporosis.
| HMTs and HMDs | Target histone sites | Target genes | Function |
|---|---|---|---|
| PRMT1/PRMT4 (CARM1) | H4R3me2a, H3R17me2a | CYP24A1 | Activates CYP24A1 gene in osteoblasts (18). |
| PRMT5 | H4R3me2s (19), H3R8me2s (20) | ISG ( 19), CXCL10 and RSAD2 (20) | Regulates osteogenic differentiation of BMSCs (19). Inhibits PRMT5 from suppressing osteoclast differentiation (20). |
| PADI4 | Runx2 | Promotes osteoblast mineralization (21). | |
| KMT1A (Suv39h1) | H3K9me2/3 | Runx2 | Delays osteoblast differentiation (22). |
| KMT1C (G9a, EHMT2) | H3K9me2 (23), H3K27me1 (24) | Runx2 (23), MMP-9 (24) | Regulates proliferation and differentiation of cranial bone cells (23) Induces expression of osteoclastogenesis-related genes and promotes osteoclast differentiation (24). |
| KMT1D (EHMT1) | H3K9me2 | Runx2 | Suppresses osteogenic differentiation of mesenchymal stem cells (25). |
| KMT1E (ESET,SETDB1) | H3K9me3 | Regulates osteoblast differentiation of MSCs (26). | |
| KMT6 (EZH2) | H3K27me3 | Wnt4, Foxc1 | Enhances both osteogenesis and osteoclastogenesis (27). |
| Mll-COMPASS complexes | H3K4me3 | Runx2, p57 | Promotes Runx2, p57 gene transcription (28). |
| KMT2D (MLL4) | H3K4me1 | Runx2 | Promotes osteoblast differentiation (29). |
| KMT4 (DOT1L) | H3K9me2 | CD9, MMP-9 | Inhibits osteoclastogenesis and protects against osteoporosis (30). |
| KDM1 (LSD1) | H3K4me1 (31), H3K4me2 (29) | Runx2 (31), Wnt7b, BMP2 (29) | Inhibits osteoblast differentiation of C2C12 cells (31). Inhibits osteogenic differentiation of BMSCs (29). |
| KDM4A (JMJD2A) | H3K9me3 | Sfrp4, C/ebpα | Promotes adipogenic differentiation and inhibits osteogenic differentiation (32). |
| KDM4B (JMJD2B) | H3K9me3 | Runx2, Ccnd1 | Promotes osteogenic differentiation of BMSCs and maintains bone–fat balance (33, 34). |
| KDM5A (JARID1A, RBP2) | H3K4me3 | Runx2 | Inhibits BMP2-induced osteogenesis of MSCs (35). Inhibits osteogenic differentiation of human adipose-derived stromal cells (36). |
| KDM5B (JARID1B, PLU-1) | H3K4me3 | Runx2 | Enhances osteoblast differentiation (37). |
| KDM6A (UTX) | H3K27me3 | Inhibits adipogenic differentiation and promotes osteogenic differentiation of BMSCs (38). | |
| KDM6B (JMJD3) | H3K27me3 | Runx2, Osx (39), NFATc1 (40) | Regulates osteoblast differentiation (39).Promotes osteoclast differentiation (40). |
HDM, histone demethylase; HMT, histone methyltransferase.
PRMT, Protein arginine methyltransferase; CARM1, Coactivator associated arginine methyltransferase 1; CYP24A1, Cytochrome P450 family 24 subfamily A member 1; ISG, Interferon-stimulated gene; CXCL10, C-X-C motif chemokine ligand 10; RSAD2, Radical S-adenosyl methionine domain containing 2; PADI4, Peptidyl arginine deiminase 4; Runx2, Runt-related transcription factor 2; Suv39h1, Suppressor of variegation 3-9 homolog 1; KMT, Calmodulin-Lysine N-methyltransferase; EHMT, Euchromatic histone lysine methyltransferase; MMP, Matrix metallopeptidase; ESET,SETDB1, SET domain bifurcated histone lysine methyltransferase; EZH2, Enhancer of zeste 2 polycomb Repressive Complex 2 Subunit; Foxc1, Forkhead box C1; DOT1L, DOT1 Like Histone Lysine Methyltransferase; KDM, LSD, Lysine demethylase; BMP2, Bone morphogenetic protein 2; JMJD, JmjC domain-containing histone demethylation protein; Sfrp4, Secreted frizzled related protein 4; C/ebpα, CCAAT enhancer binding protein alpha; Ccnd1, Cyclin D1; RBP2, Retinol binding protein 2; UTX, Utx histone demethylase; Osx, Osterix; NFATc1, Nuclear factor of activated T cells 1.