1 research outputs found
A Mechanism of Cohesin-Dependent Loop Extrusion Organizes Zygotic Genome Architecture
Abstract Fertilization triggers assembly of higherâorder chromatin structure from a condensed maternal and a naĂŻve paternal genome to generate a totipotent embryo. Chromatin loops and domains have been detected in mouse zygotes by singleânucleus HiâC (snHiâC), but not bulk HiâC. It is therefore unclear when and how embryonic chromatin conformations are assembled. Here, we investigated whether a mechanism of cohesinâdependent loop extrusion generates higherâorder chromatin structures within the oneâcell embryo. Using snHiâC of mouse knockout embryos, we demonstrate that the zygotic genome folds into loops and domains that critically depend on Scc1âcohesin and that are regulated in size and linear density by Wapl. Remarkably, we discovered distinct effects on maternal and paternal chromatin loop sizes, likely reflecting differences in loop extrusion dynamics and epigenetic reprogramming. Dynamic polymer models of chromosomes reproduce changes in snHiâC, suggesting a mechanism where cohesin locally compacts chromatin by active loop extrusion, whose processivity is controlled by Wapl. Our simulations and experimental data provide evidence that cohesinâdependent loop extrusion organizes mammalian genomes over multiple scales from the oneâcell embryo onward