Whole-genome DNA methylation in skin lesions from patients with psoriasis vulgaris

Psoriasis, a chronic inflammatory skin disorder, is characterized by aberrant keratinocyte proliferation and differentiation in the epidermis. Although the pathogenesis of psoriasis is still incompletely understood, both genetic susceptibilities and environmental triggers are known to act as key players in its development. Several studies have suggested that DNA methylation is involved in the pathogenesis of psoriasis. However, the precise mechanisms underlying the regulation and maintenance of the methylome as well as their relationship with this disease remain poorly characterized. Herein, we used methylated DNA immunoprecipitation sequencing (MeDIP-Seq) to characterize whole-genome DNA methylation patterns in involved and uninvolved skin lesions from patients with psoriasis. The results of our MeDIP-Seq analyses identified differentially methylated regions (DMRs) covering almost the entire genome with sufficient depth and high resolution, showing that the number of hypermethylated DMRs was considerably higher than that of hypomethylated DMRs in involved psoriatic skin samples. Moreover, gene ontology analysis of MeDIP-Seq data showed that the aberrantly methylated genes belonged to several different ontological domains, such as the immune system, cell cycle and apoptosis. The results of the bisulfite-sequencing experiments for the genes PDCD5 and TIMP2 confirmed the methylation status identified by MeDIP-Seq, and the mRNA expression levels of these two genes were consistent with their DNA methylation profiles. To our knowledge, the present study constitutes the first report on MeDIP-Seq in psoriasis. The identification of whole-genome DNA methylation patterns associated with psoriasis provides new insight into the pathogenesis of this complex disease and represents a promising avenue through which to investigate novel therapeutic approaches.

► We firstly applied MeDIP-Seq to measure methylation patterns in psoriatic lesions. ► A comprehensive and detailed picture of methylation patterns was obtained. ► Bisulfite sequencing validated DNA methylation patterns at PDCD5 and TIMP2 loci. ► Expression of PDCD5 and TIMP2 correlates with its DNA methylation levels.