Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea.
Arch Dermatol Res. 2014 Apr;306(3):259-68. doi: 10.1007/s00403-013-1432-8. Epub 2013 Dec 10.
Psoriasis is a chronic inflammatory skin disease that is characterized by aberrant cross-talk between keratinocytes and immune cells such as CD4+ T cells, resulting in keratinocyte hyperproliferation in the epidermis. DNA methylation, one of several epigenetic mechanisms, plays an important role in gene expression without changing the DNA sequence. Several studies have suggested the involvement of epigenetic regulation in skin lesions from patients with psoriasis. In this study, we investigated the genome-wide DNA methylation status of CD4+ T cells in patients with psoriasis compared with healthy subjects using methylated DNA immunoprecipitation sequencing (MeDIP-Seq). The results of MeDIP-Seq showed that the global methylation values of CD4+ T cells are higher in patients with psoriasis than in healthy controls, particularly in the promoter regions. Among the most hypermethylated genes in the promoter regions, we selected the genes whose expression is significantly reduced in the CD4+ T cells of psoriasis patients. Studies using the methylation inhibitor 5-azacytidine in vitro methylation assays have shown that the differential expression levels were associated with the methylation status of each gene. Bisulfite sequencing of the transcription start region of phosphatidic acid phosphatase type 2 domain containing 3 (PPAPDC3), one of the selected genes, showed hypermethylation in the CD4+ T cells of psoriasis patients. These results suggested that the methylation status, which is identified by MeDIP-Seq of the genes, was correlated with the mRNA expression level of the genes. Collectively, the DNA methylation status in CD4+ T cells might be associated with the pathogenesis of psoriasis.
银屑病是一种慢性炎症性皮肤病，其特征是角质形成细胞和免疫细胞（如 CD4+T 细胞）之间的异常串扰，导致表皮角质形成细胞过度增殖。DNA 甲基化是几种表观遗传机制之一，它在不改变 DNA 序列的情况下对基因表达起着重要作用。几项研究表明，表观遗传调控参与了银屑病患者的皮肤损伤。在这项研究中，我们使用甲基化 DNA 免疫沉淀测序（MeDIP-Seq），比较了银屑病患者和健康对照者 CD4+T 细胞的全基因组 DNA 甲基化状态。MeDIP-Seq 的结果表明，银屑病患者 CD4+T 细胞的整体甲基化值高于健康对照组，特别是在启动子区域。在启动子区域中甲基化程度最高的基因中，我们选择了在银屑病患者 CD4+T 细胞中表达明显降低的基因。使用体外甲基化测定法中的甲基化抑制剂 5-氮杂胞苷进行的研究表明，差异表达水平与每个基因的甲基化状态相关。所选基因之一的磷酸脂酸磷酸酶 2 结构域包含 3（PPAPDC3）转录起始区的亚硫酸氢盐测序显示，银屑病患者的 CD4+T 细胞中存在高甲基化。这些结果表明，通过 MeDIP-Seq 鉴定的基因的甲基化状态与基因的 mRNA 表达水平相关。总之，CD4+T 细胞中的 DNA 甲基化状态可能与银屑病的发病机制有关。
