DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project

• Published in: PLoS biology Vol. 2; no. 12; p. e405
• Main Authors: Rakyan, Vardhman K, Hildmann, Thomas, Novik, Karen L, Lewin, Jörn, Tost, Jörg, Cox, Antony V, Andrews, T Dan, Howe, Kevin L, Otto, Thomas, Olek, Alexander, Fischer, Judith, Gut, Ivo G, Berlin, Kurt, Beck, Stephan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.12.2004; Public Library of Science (PLoS)
• Subjects: Bioinformatics/Computational Biology; Comparative analysis; CpG Islands; Cytosine - metabolism; Databases, Genetic; Deoxyribonucleic acid; DNA; DNA Methylation; Epigenesis, Genetic; Epigenetics; Exons; Gene Expression Regulation; Genetic Variation; Genetics; Genetics/Genomics/Gene Therapy; Genome, Human; Genomes; Genomics; Homo (Human); Human Genome Project; Humans; Immunology; Internet; Introns; Major Histocompatibility Complex - genetics; Mass Spectrometry; Molecular Biology/Structural Biology; Pilot Projects; Polymerase Chain Reaction; RNA, Messenger - metabolism; Sequence Analysis, DNA; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Statistical analysis; Sulfites - chemistry; Tissue Distribution; Sulfites; Major Histocompatibility Complex; Exons; Introns; Epigenesis, Genetic; Humans; Gene Expression Regulation; Databases, Genetic; Sequence Analysis, DNA; Genetic Variation; Tissue Distribution; DNA Methylation; Pilot Projects; Mass Spectrometry; Polymerase Chain Reaction; CpG Islands; Cytosine; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Internet; Genome, Human; Human Genome Project; RNA, Messenger
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.0020405

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.