Polymer simulations for predicting chromatin interactions after enhancer hijacking
Many cancers arise after genome rearrangements, where breaks in the DNA are incorrectly repaired resulting in aberrations such as chromosome translocations, insertions or deletions. This can lead to enhancer hijacking events, where an enhancer or super-enhancer is relocated, and then drives overexpression of a gene in its new location. The gene can be converted into an oncogene, which subsequently leads to disease. It is thought that the enhancers drive expression by interacting with promoters through chromatin looping. To understand enhancer hijacking, we need to understand the nature of these interactions, however characterising these experimentally is difficult. Chromatin and 3D structural profiling methods are difficult to apply to very small clinical human tissue samples, and the small (<1kbp) interacting genomic regions within super-enhancers (which can be 100s of kbp long) are difficult to identify. Here I will present our work using polymer physics based modelling to predict oncogene promoter-enhancer interactions in rearranged genomes. The model not only provides information to help target the interacting sites in the lab, but also reveals new mechanistic understanding on the process of enhancer hijacking.