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DNA methylation profiling of the human major histocompatibility complex: A pilot study for the Human Epigenome Project

Rakyan, VK; Hildmann, T; Novik, KL; Lewin, J; Tost, J; Cox, AV; Andrews, TD; ... Beck, S; + view all (2004) DNA methylation profiling of the human major histocompatibility complex: A pilot study for the Human Epigenome Project. PLOS BIOL , 2 (12) , Article e405. 10.1371/journal.pbio.0020405. Green open access

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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.

Type: Article
Title: DNA methylation profiling of the human major histocompatibility complex: A pilot study for the Human Epigenome Project
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pbio.0020405
Publisher version: http://dx.doi.org/10.1371/journal.pbio.0020405
Language: English
Additional information: © 2004 Rakyan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: CPG ISLANDS, TRANSLATIONAL REGULATION, SEQUENCE, CANCER, EXPRESSION, PATTERNS, MUSCLE, GENES, MOUSE, MAP
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/6721
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