DNA methylation profiling of the human major histocompatibility complex: A pilot study for the Human Epigenome Project
DNA methylation profiling of the human major histocompatibility complex: A pilot study for the Human Epigenome Project
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DOI：
10.1371/journal.pbio.0020405
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发表时间：
2004-12-01
期刊：
影响因子：
9.8
通讯作者：
Beck, S
中科院分区：
文献类型：
--
作者：
Rakyan, VK;Hildmann, T;Beck, S
人类表观基因组计划旨在识别、编目和解释全基因组 DNA 甲基化现象。 DNA 甲基化自然发生在胞嘧啶-鸟嘌呤二核苷酸的胞嘧啶碱基上，与多种生物过程和许多疾病的病因学密切相关。差异甲基化胞嘧啶产生不同的特征，被认为是基因活性、组织类型和疾病状态所特有的。此类甲基化可变位点的识别将显着提高我们对基因组生物学的理解和诊断疾病的能力。在这里，我们报告了人类表观基因组计划试点研究的结果，其中需要对人类主要组织相容性复合物进行甲基化分析。这项研究涉及使用亚硫酸氢盐 DNA 测序开发用于高通量甲基化分析的集成管道，发现甲基化可变位置，通过基质辅助激光解吸/电离质谱法进行表观基因分型，以及开发一个集成的公共数据库（可在 http://www.epigenome.org 上获取）。我们对主要组织相容性复合体中的 DNA 甲基化水平进行分析，包括与多个组织和个体中 90 个基因相关的调控外显子和内含子区域，揭示了甲基化谱的双峰分布（即绝大多数分析区域要么低甲基化，要么高甲基化）、组织特异性、个体间变异以及与独立基因表达数据的相关性。
The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine-guanine dinucleotides, DNA methylation is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated), tissue specificity, inter-individual variation, and correlation with independent gene expression data.