Landscape of Cohesin-Mediated Chromatin Loops in the Human Genome

Fabian Grubert, Rohith Srivas, Damek V. Spacek, Maya Kasowski, Mariana Ruiz Velasco, Nasa Sinnott-Armstrong, Peyton Greenside, Anil Narasimha, Qing Liu, Benjamin Geller, Akshay Sanghi, Michael Kulik, Silin Sa, Marlene Rabinovitch, Anshul Kundaje, Stephen Dalton, Judith Zaugg, Michael Snyder.
Physical interactions between distal regulatory elements play a key role in regulating gene expression, yet the extent to which these interactions vary between cell types and contribute to cell type-specific gene expression remains unclear. To address these questions as part of ENCODE Phase III, we mapped cohesin-mediated chromatin loops, using a high-resolution ChIA-PET assay, and gene expression in 24 diverse human cell types, including core ENCODE cell lines. We find 28% of all chromatin loops vary across cell types; these variations correlate with changes in gene expression and are effective at grouping cell types based on their tissue of origin. The connectivity of genes corresponds to different functional classes, with house-keeping genes having few contacts, and dosage-sensitive genes being highly connected to enhancer elements. Our results provide important insights on how variation in 3D chromatin organization corresponds to cell type-specific function and identity. This atlas of chromatin loops complements the diverse maps of regulatory architecture that comprise the ENCODE Encyclopedia to advance emerging analyses of genome structure and function.