Table 2.
Epigenetic enzymes related to inflammation after injury.
Enzyme | Alteration after injury | Molecular effect | Effect on gene expression | Genes altered | Direct relation to pain | Reference |
---|---|---|---|---|---|---|
EZH2 | Increased | Di- and tri-methylation of H3K27 | Gene silencing | Indirect increase of TNF-α, IL-1β, and MCP-1 | Yes | Arifuzzaman et al., 2017; Yadav and Weng, 2017 |
JMJD3 | Increased | Demethylation of H3K27me2/3 | De-repression | IL-6, BDNF | No | Lee et al., 2012; Palomer et al., 2016 |
MeCP2 | Increased | Binding to CpG | Gene silencing | Indirect increase of IL-6, TNF-α, CXCL2, CXCL3, and CSF3 | Yes | Wang et al., 2011; Tochiki et al., 2012; Cronk et al., 2015 |
DNMT3B | Decreased | CpG methylation | Gene silencing | CXC3R3 | Yes | Jiang et al., 2017 |
HATs | Increased | H3K9 acetylation | Gene expression | CCL2 (MCP-1), CCL3 (MIP-1a), MiP-2, VEGFA, CXCR2, CXCR1/CXRR5, VEGFR, BDNF, COX2 | Yes | Kiguchi et al., 2012, 2013, 2014; Sun et al., 2013; Zhu et al., 2014 |
HDAC1 | Increased | H3K9 hypoacetylation | Reduction of gene expression | Yes | Kami et al., 2016 | |
SIRT1 | Decreased | H3 deacetylation | Reduction of gene expression | IL-6, INF-γ, IL-1β, TNF-α, and nuclear factor-kappa B (NF-κB) p65 activation | Yes | Yin et al., 2013; He et al., 2014; Shao et al., 2014; Gui et al., 2015 |
SIRT2 | Decreased | H3 deacetylation | Reduction of gene expression | TNF-α, IL-1β, and IL-6, and acetylation of the NF-κB p65 | Yes | Zhang and Chi, 2017 |
BET proteins | Unkown | Binding to acetylated histones | Gene expression | Cytokines, chemokines | No | Huang et al., 2009; Nicodeme et al., 2010; Gallagher et al., 2014 |