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Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding. CTCF remains essential for TAD organization in non-dividing cells. Surprisingly, active and inactive genome compartments remain properly segregated  upon CTCF depletion, revealing that compartmentalization of mammalian chromosomes emerges independently of proper insulation of TADs. Furthermore, our data support that CTCF mediates transcriptional insulator function through enhancer blocking but not as a direct barrier to heterochromatin spreading. Beyond defining the functions of CTCF in chromosome folding, these results provide new fundamental insights into the rules governing mammalian genome organization.", "journal": "Cell", "uuid": "1ec54a03-0aaa-4d17-91d5-7a6ae3b12157", "authors": ["Nora EP", "Goloborodko A", "Valton AL", "Gibcus JH", "Uebersohn A", "Abdennur N", "Dekker J", "Mirny LA", "Bruneau BG"], "@id": "/publications/1ec54a03-0aaa-4d17-91d5-7a6ae3b12157/", "display_title": "Nora EP et al. (2017) PMID:28525758", "title": "Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 3, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSUP5QTXB/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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."}}}, {"parent": "/biosamples/4DNBSSXDB84N/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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."}}}, {"parent": "/biosamples/4DNBSWXKXWMN/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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": []}