TABLE 1.

Mechanisms and clinical values of histone modification in wound healing.

Modification classification	Enzymes	Target histone	Mechanism	Clinical value	Ref.
Histone methylation	MLL1	H3K4me3	Up-regulate macrophage-mediated inflammation via NF-kB	Promote wound healing	Kimball et al. (2017)
Histone methylation	MLL1	H3K4me3	Up-regulate TLR4 expression in myeloid cells and control the inflammatory response	Promote wound healing	Davis et al. (2019)
Histone methylation	MLL1	H3K4me3	Up-regulated TLR4 expression in macrophage and increase proinflammatory cytokines expression of macrophage	Impair diabetic wound healing	Davis et al. (2020a)
Histone methylation	Setdb2	H3K9me3	Inhibit the production of NF-κB-mediated inflammatory cytokines and XO-mediated UA in macrophages	Regulate normal transition of macrophage phenotype and improve wound healing	Kimball et al. (2019)
Histone demethylation	N/A	H3K9me2 and H3K27me3	Reverse diabetes-induced histone methylation of the ER β promoter and suppression of NRF1 and SOD2	Epigenetic modification of HSC could be used to promote wound healing.	Xie et al. (2021)
Histone demethylation	Jmjd3	H3K27me3	Shape programmed macrophages toward a proinflammatory phenotype	Impair wound healing	Gallagher et al. (2015)
Histone demethylation	Jmjd3	H3K27me3	Up-regulate NFκB-mediated inflammatory genes in macrophage	Shape macrophage toward proinflammatory state and impair diabetic wound healing	Davis et al. (2020b)
Histone methylation	PcGs	H3K27me3	Silence repair genes including Myc and Egfr	Inhibit wound re-epithelialization	Shaw and Martin, (2009)
Histone demethylation	JMJD3	H3K27me3	Enhance keratinocyte migration by increasing Notch 1 gene expression	Accelerate wound healing.	Na et al. (2017)
Histone methylation	SETD2	H3K36me3	Inhibit keratinocyte proliferation and migration via down-regulate AKT/mTOR signalling	Impair wound healing	Li et al. (2021a)
Histones acetylation	N/A	H3K9ac	Accelerate epithelial migration and active terminal differentiation of KC stem cells	PBMT could accelerate wound healing by up-regulating histones acetylation	Martins et al. (2021)
Histone acetylation	MOF	H4K16ac	Promote NF-κB-mediated inflammatory gene transcription in diabetic wound macrophages	MOF-knockout might accelerate diabetic wound healing	den Dekker et al. (2020)
Histone deacetylation	HDACs	N/A	Increase proinflammatory Ly6Chigh monocytes	HDAC inhibitor could increase repairing Ly6Clow subsets and enhance wound healing	Cabanel et al. (2019)
Histone deacetylation	HDAC6	N/A	HDAC6 inhibitor-TSA hydrogel inhibited IL-1β secretion of macrophages and up-regulated IL-10 level	TSA could accelerate wound healing	Karnam et al. (2020)