The critical importance of epigenetics in autoimmune-related skin diseases

Genetic and Epigenetic Mechanisms of Psoriasis

“…DNA methylation in psoriasis has been shown to occur in multiple immune active locations besides the skin and has been linked to disease severity, distribution of lesions and different tissue types implicated [ 105 ]. Epigenome-wide methylation studies have discovered differentially methylated genes and pathways in psoriatic lesions compared with healthy controls or psoriatic lesions compared with the non-lesional skin of psoriatic patients [ 69 , 106 , 107 , 108 ]. However, compared with psoriatic lesions, the methylation pattern of non-lesional skin of psoriatic patients was more similar to that of healthy patients [ 105 ].…”

“…When comparing psoriasis-involved skin to the adjacent normal skin of patients with psoriasis, differentially methylated CpGs are found, some of which situated at the promoters of known PSORS genes, such as S100A9, PTPN22, SELENBP1, CARD14 , and KAZN [ 108 ]. Characteristically, psoriatic skin with Munro’s microabscess has shown to be abundant in differentially methylated genes related to neutrophil chemotaxis, suggesting that the DNA methylation profile can also be related with psoriasis histopathological features [ 108 ].…”

“…When comparing psoriasis-involved skin to the adjacent normal skin of patients with psoriasis, differentially methylated CpGs are found, some of which situated at the promoters of known PSORS genes, such as S100A9, PTPN22, SELENBP1, CARD14 , and KAZN [ 108 ]. Characteristically, psoriatic skin with Munro’s microabscess has shown to be abundant in differentially methylated genes related to neutrophil chemotaxis, suggesting that the DNA methylation profile can also be related with psoriasis histopathological features [ 108 ]. Other differentially methylated loci in psoriatic lesions compared with the normal skin of patients with psoriasis and with normal skin from healthy controls are S100A8 (involved in epidermal differentiation), CYP2S1 (metabolism of retinoic acid), and EIF2C2 (with a role in RNA processing) [ 107 ].…”

“…H1 histones serve as linkers of DNA on the entry and exit sites of nucleosomes. Post-transcriptional modifications of histones can change the accessibility of DNA sequences and consequently alter their transcription [ 108 ]. Several histone modifications have been described in psoriasis skin with potential pathogenetic implications.…”

“…As compared with healthy skin, lesional psoriasis skin exhibits dysregulated histone acetyltransferases (HATs) and histone deacetylases (HDACs), the enzymes that sustain the general equilibrium between histone acetylation and deacetylation [ 108 ]. In fact, HDAC-1 has been found to be upregulated in psoriatic skin, which could induce the over-expression of VEGF, proliferation of endothelial cells, and keratinocyte survival [ 121 ].…”