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. [Display omitted] •Cohesin-powered chromatin jets emerge from focal areas of accessible chromatin•Unless constrained by CTCF, jets can propagate symmetrically for 1–2 Mb•CTCF can block jets or deflect the angle of jet propagation•These data suggest that loop extrusion is controlled independently in both directions Cohesin organizes the genome in 3D nuclear space. In this issue of Molecular Cell, Guo et al. describe and characterize “jets,” an unusual form of cohesin-mediated chromatin interactions. Jets offer insights into the physiological behavior of cohesin-mediated loop extrusion and the principles that underlie genome organization.