| Epigenetic Regulation of Filaggrin Gene Expression in Human Epidermal Keratinocytes | |
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| 년도 | 2020 |
| 날짜 | 2020 Apr |
| 페이지 / 학회지명 |
32(2), 122-129 / Annals of Dermatology |
| 논문저자 | Jaehyouk Lee 1 2, Ara Jang 1 2, Seong Jun Seo 3, Soon Chul Myung 1 2 |
| Link |
https://anndermatol.org/DOIx.php?id=10.5021/ad.2020.32.2.122
90회 연결
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1 Bio-Integration Research Center for Nutra-Pharmaceutical Epigenetics, Chung-Ang University, Seoul, Korea. 2 Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea. 3 Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea. Abstract Background: Loss-of-function mutations in the filaggrin gene (FLG), which encodes an epidermal protein crucial for the formation of a functional skin barrier, have been identified as a major predisposing factor in the etiopathogenesis of atopic dermatitis (AD). Recent reports of relatively low frequencies of FLG-null mutations among specific ethnic groups with AD necessitated analysis of the epigenetic regulation which may control FLG expression without altering its DNA sequence. Objective: The study aimed to identify DNA methylation-dependent regulation of FLG expression. Methods: Quantitative polymerase chain reaction was performed to determine the restoration of FLG mRNA expression in normal human epidermal keratinocyte (NHEK) cells after treatment with epigenetic modulating agents. Bisulfite genomic sequencing and pyrosequencing analyses of the FLG promoter region were conducted to identify the citical CpG sites relevant to FLG expression. We performed small-scale pilot study for epidermal tissues obtained from Korean patients with severe AD. Results: We here show that DNA methylation in the FLG with non-CpG island promoter is responsible for the transcriptional regulation of FLG in undifferentiated NHEK cells. The methylation frequencies in a single CpG site of the FLG promoter were significantly higher in lesional epidermis than those in matched nonlesional epidermis of subjects with severe AD. Conclusion: Our in vitro and clinical studies point to this unique CpG site as a potential DNA methylation marker of FLG, which can be a promising therapeutic target in the complications of filaggrin-related skin barrier dysfunction as well as in AD. Keywords: Atopic dermatitis; DNA methylation; Keratinocyte. |
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