Table 1.

Summary of epigenetic modifications in SSc.

Epigenetic process	Modification	Cell type	Effect	References
Global DNA methylation
	↓	Fibroblasts	Profibrotic	Altorok et al.25
	↓	CD4+ T cells	Supposed increased expression of autoimmune-related genes in lymphocytes	Lei et al.34
	Skewed X chromosome inactivation	PBMCs	Immunosenescence, autoantibody production	Kanaan et al.43
				Ozbalkan et al.44
Gene-specific DNA methylation
Fli1	↑	Fibroblasts	Profibrotic	Wang et al.26
KLF5	↑	Fibroblasts	Profibrotic	Noda et al.29
DKK1, SFRP1	↑	Fibroblasts	Profibrotic	Dees et al.31
PARP1	↑	Fibroblasts	Profibrotic	Zhang et al.32
IFN-related genes (IFI44L, IFITM1, MX1, PARP9)	↓	CD4+ and CD8+ T cells	Increased IFN production	Ding et al.35
				Chen et al.36
IRF7	↓	PBMCs	N.D.	Rezaei et al.38
ITGAL	↓	CD4+ T cells	Increased proliferation of CD4+ T cells, IgG overproduction by B cells, and excessive collagen synthesis by fibroblasts	Wang et al.39
RUNX3	↑	pDCs	Profibrotic	Affandi et al.40
BMPR2	↑	MVECs	Proapoptotic	Wang and Kahaleh42
CD40L (X chromosome)	↓	CD4+ T cells	Altered immune response	Lian et al.45
ARX, HSFX1, IL1RAPL2 (X chromosome)	↑	PBMCs	Disease susceptibility	Selmi et al.46
ZBED1, ZNF41, PGMRC1 (X chromosome)	↓	PBMCs	Disease susceptibility	Selmi et al.46
FOXP3 (X chromosome)	↑	CD4+ T cells	Treg reduction	Wang et al.47
Global histone acetylation
	↓ HDAC2, HDAC7 H4 hyperacetylation	B cells	B cell dysfunction	Wang et al.48
	altered H3K4me3, H3K27ac	Monocytes	Altered phenotype	Van der Kroef et al.49
	↑ HDAC5	Endothelial cells	Impaired angiogenesis	Tsou et al.50
	↓ SIRT1, 3, 7	Fibroblasts	Profibrotic	Chu et al.51
				Wyman et al.52
				Sosulski et al.53
	↑ p300	Fibroblasts	Profibrotic	Ghosh et al.54
Gene-specific histone acetylation
KLF5	H3, H4 hypoacetylation	Fibroblasts	Profibrotic	Noda et al.29
FLI1	H3, H4 hypoacetylation	Fibroblasts	Profibrotic	Noda et al.29
				Wang et al.55
Global histone methylation
	↑ H3K27me3 ↑ EZH2	Fibroblasts, endothelial cells	Profibrotic, impaired angiogenesis	Xiao et al.56
				Tsou et al.57
	↑ H3K27me3 ↑ EZH2	Fibroblasts	Antifibrotic	Krämer et al.58
	↓ H3K27me3 ↑ JMJD3	CD4+ T cells	N.D.	Wang et al.59
	H3K9 hypomethylation ↓ SUV39H2 ↑ JHDM2	B cells	N.D.	Wang et al.48
Gene-specific histone methylation
FOSL2	↓ H3K27me3 ↑ JMJD3 = UTX	Fibroblasts	Profibrotic	Bergmann et al.60

PBMC, peripheral blood mononuclear cell; pDC, plasmacytoid dendritic cell: MVEC, microvascular endothelial cell; N.D., not determined; SSc, systemic sclerosis.