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(2017)", "title": "A mechanism of cohesin-dependent loop extrusion organizes zygotic genome architecture.", "uuid": "856a6952-ecc0-4bbf-9e6d-77d07652624f", "abstract": "Fertilization triggers assembly of higher-order chromatin structure from a condensed maternal and a naive paternal genome to generate a totipotent embryo. Chromatin loops and domains have been detected in mouse zygotes by single-nucleus Hi-C (snHi-C), but not bulk Hi-C. It is therefore unclear when and how embryonic  chromatin conformations are assembled. Here, we investigated whether a mechanism  of cohesin-dependent loop extrusion generates higher-order chromatin structures within the one-cell embryo. Using snHi-C of mouse knockout embryos, we demonstrate that the zygotic genome folds into loops and domains that critically  depend on Scc1-cohesin 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 snHi-C, 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 cohesin-dependent loop extrusion organizes mammalian genomes over multiple scales from the one-cell embryo onward.", "display_title": "Gassler J et al. (2017) PMID:29217590", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"title": "A mechanism of cohesin-dependent loop extrusion organizes zygotic genome architecture.", "uuid": "856a6952-ecc0-4bbf-9e6d-77d07652624f", "display_title": "Gassler J et al. (2017) PMID:29217590", "@type": ["Publication", "Item"], "journal": "The EMBO journal", "abstract": "Fertilization triggers assembly of higher-order chromatin structure from a condensed maternal and a naive paternal genome to generate a totipotent embryo. Chromatin loops and domains have been detected in mouse zygotes by single-nucleus Hi-C (snHi-C), but not bulk Hi-C. It is therefore unclear when and how embryonic  chromatin conformations are assembled. Here, we investigated whether a mechanism  of cohesin-dependent loop extrusion generates higher-order chromatin structures within the one-cell embryo. Using snHi-C of mouse knockout embryos, we demonstrate that the zygotic genome folds into loops and domains that critically  depend on Scc1-cohesin 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 snHi-C, 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 cohesin-dependent loop extrusion organizes mammalian genomes over multiple scales from the one-cell embryo onward.", "ID": "PMID:29217590", "@id": "/publications/856a6952-ecc0-4bbf-9e6d-77d07652624f/", "status": "current", "authors": ["Gassler J", "Brandao HB", "Imakaev M", "Flyamer IM", "Ladstatter S", "Bickmore WA", "Peters JM", "Mirny LA", "Tachibana K"], "date_published": "2017-12-07", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 13, "@context": "/terms/", "aggregated-items": {"badges": []}, "validation-errors": []}