During the past four years, Manel Esteller’s lab has published the results and hypotheses in journals including Nature Genetics, Science, Nature Cell Biology, EMBO Journal, Journal of the National Cancer Institute, Proceedings of the National Academy of Sciences U.S.A., EMBO Reports, Cell Cycle, etc., among others. The laboratory has two major interests: a) analysis and identification of aberrant DNA methylation in Cancer. This study has two levels: CpG islands hypermethylation analysis in the candidate gene analysis of the promoters of candidate tumor suppressor and DNA repair genes, and use of epigenomic techniques to identify novel targets and their role in molecular diagnostics; b) study of chromatin alterations in cancer, including the analysis of histone acetyltransferases, deacetylases and chromatin remodelling factors in human neoplasia, and their implications for the development of novel therapeutic strategies.

In the context of the CANCERDIP proposal, the main task of our laboratory is the epigenetic characterisation of model systems and patient material performed at several levels: I) Global analysis: Analysis of 5-methylcytosine content by high performance capillary electrophoresis (HPCE), global analysis of histone modification changes by HPCE. II) Gene-specific analysis: 1. DNA methylation analysis by bisulfite genomic sequencing candidate genes; 2. chromatin immunoprecipitation (ChIP) assays. Antibodies directed against different post-translational modifications of histones will be used (di- and tri- methylK4 H3, K9 H3, K27 H3, K20 H4). Following chromatin immunoprecipitation, primers corresponding to these genes, for which their methylation status will also be characterized, will be used to investigate the recruitment to their promoters. 3. Genome-wide analysis of promoter hypermethylation, including Amplification of Intermethylated Sites (AIMS) and 5- methyl-DNA immunoprecipitation (MeDIP) analysis followed by hybridization of genomic microarrays. 4. genome-wide analysis of histone modification changes by ChIP assays coupled to hybridization of genomic microarrays. The laboratory and the Bellvitge Institute for Biomedical Research is equipped with all the instruments and technologies, e.g. state-of-the-art microarray, sequencing, cytogenetics and proteomics facilities necessary to perform those studies.