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首页> 外文期刊>The Journal of investigative dermatology. >Correlation between Reversal of DNA Methylation and Clinical Symptoms in Psoriatic Epidermis Following Narrow-Band UVB Phototherapy
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Correlation between Reversal of DNA Methylation and Clinical Symptoms in Psoriatic Epidermis Following Narrow-Band UVB Phototherapy

机译：窄带UVB光疗后牛皮癣表皮DNA甲基化逆转与临床症状的相关性

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摘要

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.
机译：DNA甲基化引起的表观遗传修饰与多种疾病有关。之前的学习。牛皮癣的病因集中在免疫细胞或包括基质相关变化在内的总皮肤活检中的表观遗传学变化。为了增进我们对DNA甲基化在牛皮癣中作用的理解，我们寻求获得针对牛皮癣的表皮成分的全面的DNA甲基化标记，并分析治疗期间的甲基化变化。与对照组相比，来自12位接受窄带UVB光疗的患者和12位相应健康对照的表皮细胞全基因组DNA甲基化谱图显示了牛皮癣的独特DNA甲基化模式。在牛皮癣患者样品中总共鉴定出3,665个甲基化可变位置（MVP），且总体甲基化程度较低。在患者接受光疗后，DNA甲基化模式发生了逆转，显示出卓越的临床改善。受光疗影响的MVP中只有7％（2,108个中的150个）与附近的基因表达相关。 MVPs在增强子中的富集表明牛皮癣中转录调节机制的组织特异性调节。我们的研究确定了与牛皮癣发病机理相关的关键表观遗传事件，并有助于了解人类基因组中动态DNA甲基化态势。

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