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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.", "uuid": "7343e7a5-1332-4adb-9265-cdd1381348eb", "date_published": "2017-09-27", "url": "https://www.ncbi.nlm.nih.gov/pubmed/29094699", "journal": "Nature", "title": "Two independent modes of chromatin organization revealed by cohesin removal.", "status": "current", "short_attribution": "Schwarzer W et al. (2017)", "ID": "PMID:29094699", "display_title": "Schwarzer W et al. 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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.", "date_published": "2017-09-27", "uuid": "7343e7a5-1332-4adb-9265-cdd1381348eb", "status": "current", "@id": "/publications/7343e7a5-1332-4adb-9265-cdd1381348eb/", "ID": "PMID:29094699", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 2, "@context": "/terms/", "aggregated-items": {"badges": []}, "validation-errors": []}