Table 1.
Enzymes related to epigenetic modifications of dental pulp stem cells activities
|
Proteins and their function
|
Epigenetic Targets
|
Gene manipulation of each epigenetic marker
|
Downstream targets
|
Biological process implicated
|
Reference
|
| DNA methylation | |||||
| TET1, demethylation | Gene activation | FAM20C | (↑) proliferation, (↑) odontoblast differentiation | [41-43] | |
| Histone methylation | |||||
| EHMT1, methylation | H3K9me2 | Gene repression | Runx2 | (↓) odontoblast differentiation | [51] |
| KMT2A, methylation | H3K4me3 | Gene activation | WNT5A, RUNX2, MSX2, DLX5 | (↑) odontoblast differentiation | [12,52] |
| EZH2, demethylation | H3K27me2/me3 | Gene repression | Wnt/β-Catenin pathway, IL-6, IL-8, CCL2 | (↑) Inflammation, (↓) odontoblast differentiation | [54-56] |
| KDM6B/JMJD3, demethylation | H3K27me3 | Gene repression | WNT5A, BMP2 | (↑) odontoblast differentiation | [52,58] |
| KDM5A, demethylation | H3K4me3/me2 | Gene activation | DMP1, DSPP, OSX, OCN | (↓) odontoblast differentiation | [60] |
| Histone acetylation | |||||
| p300, acetylation | H3K9ac | OCN, NANOG, SOX2, DSPP, Dmp1, Osx | (↑) pluripotency, (↑) proliferation, (↑) odontoblast differentiation | [14,64] | |
| HDAC3, deacetylation | H3K27ac | Dmp1, Osx | (↓) odontoblast differentiation | [13,66] | |
| HDAC6, deacetylation | (↓) odontoblast differentiation | [15] | |||
TET1: Ten-eleven translocation 1; EHMT1: Euchromatic histone lysine methyltransferase 1; KMT2A: Lysine methyltransferase 2A; KDM6B: Lysine demethylase 6B; KDM5A: Lysine demethylase 5A; p300: E1A binding protein p300; HDAC3: Histone deacetylase 3; HDAC6: Histone deacetylase 6; H3K9me2: Dimethylated histone H3 lysine 9; H3K4me3/me2: Tri-/di-methylated histone H3 lysine 4; H3K27me2/me3: Di-/tri-methylated histone H3 lysine 27; H3K9ac: Acetylated histone H3 lysine 9; H3K27ac: Acetylated histone H3 lysine 27; FAM20C: FAM20C golgi associated secretory pathway kinase; Runx2: RUNX family transcription factor 2; WNT5A: Wnt family member 5A; MSX2: Msh homeobox 2; DLX5: Distal-less homeobox 5; CCL2: C-C motif chemokine ligand 2; IL-6/-8: Interleukin 6/8; BMP2: Bone morphogenetic protein 2; DMP1: Dentin matrix acidic phosphoprotein 1; DSPP: Dentin sialophosphoprotein; OSX: Osterix; OCN: Osteocalcin; NANOG: Nanog homeobox; SOX2: SRY-box transcription factor 2.