BioProject

DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. More...

DNA methylation is essential for normal development and has been implicated in many pathologies including cancer. Our knowledge about genome-wide distribution of DNA methylation how it changes during cellular differentiation and how it relates to chromatin modifications in mammals remains limited. Cellular commitment to a specific lineage is controlled by differential silencing of genes which in turn depends on epigenetic processes such as DNA methylation and histone modifications. During early embryogenesis the mammalian genome is "wiped clean" of most epigenetic modifications, which are progressively re-established during embryonic development. Thus, the epigenome of each mature cellular lineage carries the record of its developmental history. Studies have revealed a relationship between methylation status and susceptibility to hypertension, cardiovascular morbidity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, obesity etc. Specific patterns of hypermethylated DNA are associated with the transcriptional silencing of genes correlating with cancer progression, and treatment response, therefore representing promising biological markers. Methylated DNA Immunoprecipitation (MeDIP) is an immunocapturing approach to isolate DNA that is methylated. The principle is that genomic DNA is randomly sheared by sonication and immunoprecipitated with an antibody that specifically recognizes 5-methylcytidine (5mc). The technique will be used to generate comprehensive DNA profiles on a genome scale and to identify abnormally methylated genes in a number of pathologic states, such as cardiovascular disease and type 2 diabetes. We intend to study DNA methylation in discordant and concordant twins, using the TWINS UK database. We will perform MeDIP in skin and fat biopsies as well as whole blood and look for differentially methylated sites. The study aims to address questions such as: to what extent is methylation heritable and what are the characteristics of heritable versus non-heritable methylated regions? Can we correlate methylation profiles with phenotypes and covariates? Can we identify novel imprinted regions? This project is in collaboration with the Department of Twin Research & Genetic Epidemiology, Kings College London. . This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ Less...