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(2017)", "@id": "/publications/c1fc12d2-5514-4ad7-963f-a572d7c51df8/", "date_published": "2017-12-15", "uuid": "c1fc12d2-5514-4ad7-963f-a572d7c51df8", "authors": ["Wutz G", "Varnai C", "Nagasaka K", "Cisneros DA", "Stocsits RR", "Tang W", "Schoenfelder S", "Jessberger G", "Muhar M", "Hossain MJ", "Walther N", "Koch B", "Kueblbeck M", "Ellenberg J", "Zuber J", "Fraser P", "Peters JM"], "abstract": "Mammalian genomes are spatially organized into compartments, topologically associating domains (TADs), and loops to facilitate gene regulation and other chromosomal functions. How compartments, TADs, and loops are generated is unknown. It has been proposed that cohesin forms TADs and loops by extruding chromatin loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here, we show that cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops.  In the absence of WAPL and PDS5 proteins, cohesin forms extended loops, presumably by passing CTCF sites, accumulates in axial chromosomal positions (vermicelli), and condenses chromosomes. Unexpectedly, PDS5 proteins are also required for boundary function. These results show that cohesin has an essential  genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed  by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA  by WAPL.", "title": "Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins.", "ID": "PMID:29217591", "@type": ["Publication", "Item"], "status": "current", "display_title": "Wutz G et al. (2017) PMID:29217591", "journal": "The EMBO journal", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"title": "Topologically associating domains and chromatin loops depend on cohesin and are regulated by CTCF, WAPL, and PDS5 proteins.", "date_published": "2017-12-15", "display_title": "Wutz G et al. (2017) PMID:29217591", "short_attribution": "Wutz G et al. (2017)", "authors": ["Wutz G", "Varnai C", "Nagasaka K", "Cisneros DA", "Stocsits RR", "Tang W", "Schoenfelder S", "Jessberger G", "Muhar M", "Hossain MJ", "Walther N", "Koch B", "Kueblbeck M", "Ellenberg J", "Zuber J", "Fraser P", "Peters JM"], "ID": "PMID:29217591", "@type": ["Publication", "Item"], "uuid": "c1fc12d2-5514-4ad7-963f-a572d7c51df8", "@id": "/publications/c1fc12d2-5514-4ad7-963f-a572d7c51df8/", "abstract": "Mammalian genomes are spatially organized into compartments, topologically associating domains (TADs), and loops to facilitate gene regulation and other chromosomal functions. How compartments, TADs, and loops are generated is unknown. It has been proposed that cohesin forms TADs and loops by extruding chromatin loops until it encounters CTCF, but direct evidence for this hypothesis is missing. Here, we show that cohesin suppresses compartments but is required for TADs and loops, that CTCF defines their boundaries, and that the cohesin unloading factor WAPL and its PDS5 binding partners control the length of loops.  In the absence of WAPL and PDS5 proteins, cohesin forms extended loops, presumably by passing CTCF sites, accumulates in axial chromosomal positions (vermicelli), and condenses chromosomes. Unexpectedly, PDS5 proteins are also required for boundary function. These results show that cohesin has an essential  genome-wide function in mediating long-range chromatin interactions and support the hypothesis that cohesin creates these by loop extrusion, until it is delayed  by CTCF in a manner dependent on PDS5 proteins, or until it is released from DNA  by WAPL.", "status": "current", "journal": "The EMBO journal", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "experiment_categorizer": {"field": "Enzyme", "value": "HindIII", "combined": "Enzyme: HindIII"}, "experiment_summary": "Dilution Hi-C on HeLa cell line with HindIII", "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSLY35NHX/", "embedded_path": "biosample.badges", "item": {"messages": ["Biosample missing culture_harvest_date", "Biosample missing doubling_number", "Biosample missing passage_number", "Biosample missing culture_duration", "Biosample missing morphology_image"], "badge": {"commendation": null, "warning": "Biosample Metadata Incomplete", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group."}}}]}, "validation-errors": []}