Genome-Wide DNA Methylation Profiling Identifies Differential Methylation in Uninvolved Psoriatic Epidermis

Abstract

Psoriasis is a chronic inflammatory skin disease with both local and systemic components. Genome-wide approaches have identified more than 60 psoriasis-susceptibility loci, but genes are estimated to explain only one-third of the heritability in psoriasis, suggesting additional, yet unidentified, sources of heritability. Epigenetic modifications have been linked to psoriasis and altered DNA methylation patterns in psoriatic versus healthy skin have been reported in whole-skin biopsies. In this study, focusing on epigenetic modifications in the psoriatic uninvolved skin, we compared the lesional and non-lesional epidermis from psoriasis patients with epidermis from healthy controls. We performed an exhaustive genome-wide DNA methylation profiling using reduced representation bisulfite sequencing, which interrogates the methylation status of approximately 3-4 million CpG sites. More than 2,000 strongly differentially methylated sites were identified and a striking overrepresentation of the Wnt and cadherin pathways among the differentially methylated sites was found. In particular, we observe a strong differential methylation in several psoriasis candidate genes. A substantial number of differentially methylated sites present in the uninvolved versus healthy epidermis suggests the presence of a pre-psoriatic state in the clinically healthy skin type. Our exploratory study represents a starting point for identifying biomarkers for psoriasis-prone skin before disease onset.

Comprehensive DNA methylation analysis of tissue of origin of plasma cell-free DNA by methylated CpG tandem amplification and sequencing (MCTA-Seq)

“…1d). We also validated the methylation values of these regions by using published DNA methylome data [8, 37, 38]. The results showed that these dmCGCGCGGs in cfDNA have a median methylation level of 42% in the liver, which is considerably higher than that in the seven other tissues ( P < 0.01, two-tailed MWW test, Fig.…”

Identifying blood-specific age-related DNA methylation markers on the Illumina MethylationEPIC® BeadChip

“…The hypomethylated CpG site linked to LOC730668, which is a Dynein Heavy Chain-Like pseudogene located on chromosome 22, has been reported in two different studies to be differentially hypomethylated in individuals with temporal lobe epilepsy, and in individuals with psoriatic epidermis [60,61] Building a prediction model for use in forensic investigations requires a small number of markers due to the minute quantities of DNA that is frequently recovered from forensic samples [64]. The six AR CpG sites selected by stepwise regression, which contained only one CpG marker that was newly added to the EPIC BeadChip, had a MAD value of 4.6 years based on the validation set.…”

Cellular scars and local crosstalk in relapsing psoriasis: an example of a skin sticking disease

“…In addition to different patterns of MHC class I expression, psoriasis patients display distinct gene expression signatures and DNA methylation profiles in non-lesional skin. 88,89 Keratinocytes from non-lesional psoriasis skin also exhibit functional differences with decreased triggering of IRF-1 and STAT1 following exposure to IFN-γ. 90 In line with decreased IFN-γ responses, supernatants from activated lesional T cells led to increased proliferation 91 and resistance against UV-induced apoptosis than healthy counterparts.…”