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Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the  absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by  loop extrusion, which helps to guide distant enhancers to their target genes.", "ID": "PMID:29094699", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "publications_of_exp": [{"date_published": "2017-09-27", "@type": ["Publication", "Item"], "uuid": "7343e7a5-1332-4adb-9265-cdd1381348eb", "ID": "PMID:29094699", "authors": ["Schwarzer W", "Abdennur N", "Goloborodko A", "Pekowska A", "Fudenberg G", "Loe-Mie Y", "Fonseca NA", "Huber W", "H Haering C", "Mirny L", "Spitz F"], "abstract": "Imaging and chromosome conformation capture studies have revealed several layers  of chromosome organization, including segregation into megabase-sized active and  inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the  absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by  loop extrusion, which helps to guide distant enhancers to their target genes.", "short_attribution": "Schwarzer W et al. 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