Objective The c-myc proto-oncogene is a general driving force in cancer. The cmyc product (Myc) is a transcription factor that binds thousands of genomic loci. However, the identity of the Myc-target genes that influence tumor development, as well as the mechanisms through which Myc acts on these genes, remain most elusive questions in the field. We will use next-generation DNA sequencing to create a multi-layered set of genome-wide profiles. We will analyze cultured mouse cells and developing tumors, the latter in a transgenic model of Myc-induced lymphoma. The profiles will include (i.) quantitative mapping of the RNA transcriptome (coding, non-coding and small RNAs), (ii.) protein-DNA interaction profiles, (iii.) epigenome profiling, (iv.) 3D-folding of genomic DNA, (v.) mutational analysis. These datasets will provide broad views and will answer pointed questions about the action of Myc. We will address the hypothesis that many Myc target genes may not be regulated at the level of net mRNA accumulation, but rather of co-transcriptional processing events. We will provide maps for the RNA-Polymerase II complex, transcriptional co-factors and histone-modifying enzymes. We will whether the Myc-binding sites that do not map within promoters may act as enhancers and/or replication origins. We will address the hypothesis that Myc contributes to reprogramming of the genome independently from its localized effects on target genes. We will also ask which genes are targets of mutations and/or epigenetic silencing in Myc-induced lymphoma. High-throughput functional genomics will be used to address which genes suppress or promote Myc-induced lymphoma. Altogether, our data will provide an unprecedented level of insight into Myc function and into the early stages of tumor progression. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncologynatural sciencesbiological sciencesgeneticsRNAnatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2010-AdG_20100317 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Coordinator ISTITUTO EUROPEO DI ONCOLOGIA SRL Address Via filodrammatici 10 20121 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Principal investigator Bruno Amati (Dr.) Administrative Contact Ilaria Foti (Ms.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all ISTITUTO EUROPEO DI ONCOLOGIA SRL Italy EU contribution € 2 494 000,00 Address Via filodrammatici 10 20121 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Principal investigator Bruno Amati (Dr.) Administrative Contact Ilaria Foti (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
