Fujio Keishi
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo.
Nihon Rinsho Meneki Gakkai Kaishi. 2016;39(1):23-9. doi: 10.2177/jsci.39.23.
Epigenetic modifications play a central role in the cellular programming of gene expression. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Recent observation that a number of GWAS SNP for immunological diseases localize to immune enhancers suggests the importance of epigenetic modifications that control enhancer activity. Epigenome-wide analysis of DNA-methylation in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) revealed differential DNA methylation in a number of disease-related gene pathways. With regard to histone mark, the requirement of millions of cells for established protocol prevents application to clinical samples. However, recent technical advances enable us to capture open chromatin in small amount of patient samples. As epigenetic modifications function as an integrator of environmental stimulation and the underlying genetic variant, detailed epigenetic analysis combined with genetic and environmental factors may facilitate the understanding of the progression of human immunological diseases.
表观遗传修饰在基因表达的细胞编程中起着核心作用。两种最具特征的表观遗传修饰是DNA甲基化和组蛋白修饰。最近观察到,许多与免疫疾病相关的全基因组关联研究(GWAS)单核苷酸多态性(SNP)定位于免疫增强子,这表明控制增强子活性的表观遗传修饰具有重要意义。对系统性红斑狼疮(SLE)和类风湿关节炎(RA)进行的全表观基因组DNA甲基化分析揭示了许多疾病相关基因途径中的DNA甲基化差异。关于组蛋白标记,既定方案需要数百万个细胞,这使得其无法应用于临床样本。然而,最近的技术进步使我们能够在少量患者样本中捕获开放染色质。由于表观遗传修饰作为环境刺激和潜在遗传变异的整合者,结合遗传和环境因素进行详细的表观遗传分析可能有助于理解人类免疫疾病的进展。