Functional screening of essential hubs

To illuminate their structural importance of non-coding loci, we chose to start with genomic regions forming large number of 3D contacts, referred to as hubs, and identify their essentials for cell viability. These hubs are mostly located in the heterochromatin regions without harboring any known functional element, but we found their formations tend to correlate with genetic variations (GVs) in cancer. Using a CRISPR-mediated deletion screening, we identified dozens of hubs that were essential for cell viability. Hi-C and single cell transcriptomic analyses showed that deletions of these essential hubs could impact critical genes located extremely distal from the hubs, which were critical for cell survival, resulting in cell death.