Chromatin jets define the properties of cohesin-driven in vivo loop extrusion

Complex genomes show intricate organization in three-dimensional (3D) nuclear space. Current models posit that cohesin extrudes loops to form self-interacting domains delimited by the DNA binding protein CTCF. Here, we describe and quantitatively characterize cohesin-propelled, jet-like chromatin contacts as landmarks of loop extrusion in quiescent mammalian lymphocytes. Experimental observations and polymer simulations indicate that narrow origins of loop extrusion favor jet formation. Unless constrained by CTCF, jets propagate symmetrically for 1-2 Mb, providing an estimate for the range of in vivo loop extrusion. Asymmetric CTCF binding deflects the angle of jet propagation as experimental evidence that cohesin-mediated loop extrusion can switch from bi- to unidirectional and is controlled independently in both directions. These data offer new insights into the physiological behavior of in vivo cohesin-mediated loop extrusion and further our understanding of the principles that underlie genome organization. Chromatin contact profiles in wild type, CD4 Cre Ctcf lox/lox and CD4 Cre Rad21 lox/lox Ctcf lox/lox immature CD4+ CD8+ double positive thymocytes were generated by in situ Hi-C, complemented by ChIP-seq of CTCF, Rad21, and H3K27ac.