Print Email Facebook Twitter 3D hotspots of recurrent retroviral insertions reveal long-range interactions with cancer genes Title 3D hotspots of recurrent retroviral insertions reveal long-range interactions with cancer genes Author Babaei, S. Akhtar, W. De Jong, J. Reinders, M.J.T. De Ridder, J. Faculty Electrical Engineering, Mathematics and Computer Science Department Intelligent Systems Date 2015-02-27 Abstract Genomically distal mutations can contribute to the deregulation of cancer genes by engaging in chromatin interactions. To study this, we overlay viral cancer-causing insertions obtained in a murine retroviral insertional mutagenesis screen with genome-wide chromatin conformation capture data. Here we find that insertions tend to cluster in 3D hotspots within the nucleus. The identified hotspots are significantly enriched for known cancer genes, and bear the expected characteristics of bona fide regulatory interactions, such as enrichment for transcription factor-binding sites. In addition, we observe a striking pattern of mutual exclusive integration. This is an indication that insertions in these loci target the same gene, either in their linear genomic vicinity or in their 3D spatial vicinity. Our findings shed new light on the repertoire of targets obtained from insertional mutagenesis screening and underline the importance of considering the genome as a 3D structure when studying effects of genomic perturbations. To reference this document use: http://resolver.tudelft.nl/uuid:d57219e8-2a27-4354-bd6b-581415023839 DOI https://doi.org/10.1038/ncomms7381 Publisher Nature Publishing Group ISSN 2041-1723 Source Nature Communications, 6, 2015 Part of collection Institutional Repository Document type journal article Rights (c) 2015 The Author(s)Creative Commons BY Files PDF deRidder_2015.pdf 6.38 MB Close viewer /islandora/object/uuid:d57219e8-2a27-4354-bd6b-581415023839/datastream/OBJ/view