title: DNA methylation profiling of the human major histocompatibility complex: a pilot study for the human epigenome project.
abstract: 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.
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom.
authors.forename: Vardhman K
authors.initials: VK
authors.lastname: Rakyan
authors.forename: Thomas
authors.initials: T
authors.lastname: Hildmann
authors.forename: Karen L
authors.initials: KL
authors.lastname: Novik
authors.forename: Jörn
authors.initials: J
authors.lastname: Lewin
authors.forename: Jörg
authors.initials: J
authors.lastname: Tost
authors.forename: Antony V
authors.initials: AV
authors.lastname: Cox
authors.forename: T Dan
authors.initials: TD
authors.lastname: Andrews
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Howe
authors.forename: Thomas
authors.initials: T
authors.lastname: Otto
authors.forename: Alexander
authors.initials: A
authors.lastname: Olek
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
authors.forename: Ivo G
authors.initials: IG
authors.lastname: Gut
authors.forename: Kurt
authors.initials: K
authors.lastname: Berlin
authors.forename: Stephan
authors.initials: S
authors.lastname: Beck
mesh_terms: D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D030541:Databases, Genetic; D044127:Epigenesis, Genetic; D005091:Exons; D005786:Gene Expression Regulation; D014644:Genetic Variation; D015894:Genome, Human; D016045:Human Genome Project; D006801:Humans; D020407:Internet; D007438:Introns; D008285:Major Histocompatibility Complex / Q000235:genetics*; D013058:Mass Spectrometry; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013447:Sulfites / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D012333:RNA, Messenger; D013447:Sulfites; D003596:Cytosine