Project description:Epigenetic aberrations are a hallmark of cancer; however, we have limited information on chromatin aberrations present in cancer cells. Here we provide genome-wide maps for histone modification binding for 6 reference histone markers in 145 cancer cell lines belonging to 9 cancer types generating 680 chromatin maps. NMF clustering for H3K27ac-defined enhancers classified cancer cells into 5 distinct subtypes. These subtypes were either correlated with the developmental trajectory of original tissue or cell phenotype such as mesenchymal features. We identify a cluster consisting of different tumor types but with a unique enhancer profile and its dependency on key oncogenes. Detailed characterization of bivalent state switches between cancer cells and their normal counterparts identified epithelial-to-mesenchymal driver transcription factors to be activated via this mechanism in breast, GBM and melanomas. Finally, we identify cancer-specific lengthening of H3K4me3 domains on oncogenes and their shortening on specific tumor-suppressors, respectively. Overall, our study provides epigenome reference maps for widely-used cancer cell lines which will be useful for discovery of important principles about chromatin mediated cancer gene regulation.
