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Correlation between Reversal of DNA Methylation and Clinical Symptoms in Psoriatic Epidermis Following Narrow-Band UVB Phototherapy.

Authors
  • Gu, Xiaolian
  • Nylander, Elisabet
  • Coates, Philip J
  • Robin Fahraeus
  • Nylander, Karin
Type
Published Article
Journal
Journal of Investigative Dermatology
Publisher
Elsevier BV
Publication Date
Aug 09, 2015
Volume
135
Issue
8
Pages
2077–2083
Identifiers
DOI: 10.1038/jid.2015.128
PMID: 25830654
PMCID: PMC4580729
Source
USPC - SET - SVS
License
Green

Abstract

Epigenetic modifications by DNA methylation are associated with a wide range of diseases. Previous studies in psoriasis have concentrated on epigenetic changes in immune cells or in total skin biopsies that include stromal-associated changes. In order to improve our understanding of the role of DNA methylation in psoriasis, we sought to obtain a comprehensive DNA methylation signature specific for the epidermal component of psoriasis and to analyze methylation changes during therapy. Genome-wide DNA methylation profiling of epidermal cells from 12 patients undergoing narrow-band UVB phototherapy and 12 corresponding healthy controls revealed a distinct DNA methylation pattern in psoriasis compared with controls. A total of 3,665 methylation variable positions (MVPs) were identified with an overall hypomethylation in psoriasis patient samples. DNA methylation pattern was reversed at the end of phototherapy in patients showing excellent clinical improvement. Only 7% of phototherapy-affected MVPs (150 out of 2,108) correlate with nearby gene expression. Enrichment of MVPs in enhancers indicates tissue-specific modulation of the transcriptional regulatory machinery in psoriasis. Our study identified key epigenetic events associated with psoriasis pathogenesis and helps understand the dynamic DNA methylation landscape in the human genome.

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