{"ID": "PMID:31168090", "lab": {"@id": "/labs/job-dekker-lab/", "uuid": "3c577664-affb-41c4-bf27-9e21c2fc1554", "status": "current", "display_title": "Job Dekker, UMMS", "correspondence": [{"contact_email": "am9iLmRla2tlckB1bWFzc21lZC5lZHU=", "@id": "/users/83b5073a-069b-4162-9b30-6f42d5551e34/", "display_title": "Job Dekker"}], "@type": ["Lab", "Item"], "title": "Job Dekker, UMMS", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.3c577664-affb-41c4-bf27-9e21c2fc1554"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/31168090", "award": {"uuid": "12a92962-8265-4fc0-b2f8-cf14f05db58b", "center_title": "External", "name": "external-award", "display_title": "EXTERNAL AWARD", "project": "External", "@type": ["Award", "Item"], "status": "current", "center": "External", "description": "Funding source is from outside 4DN.", "@id": "/awards/external-award/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Heterochromatin drives compartmentalization of inverted and conventional nuclei.", "status": "current", "aliases": ["4dn-dcic-lab:31168090"], "authors": ["Falk M", "Feodorova Y", "Naumova N", "Imakaev M", "Lajoie BR", "Leonhardt H", "Joffe B", "Dekker J", "Fudenberg G", "Solovei I", "Mirny LA"], "journal": "Nature", "abstract": "The nucleus of mammalian cells displays a distinct spatial segregation of active  euchromatic and inactive heterochromatic regions of the genome(1,2). In conventional nuclei, microscopy shows that euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery(1,2). Genome-wide chromosome conformation capture (Hi-C) analyses show this segregation as a plaid  pattern of contact enrichment within euchromatin and heterochromatin compartments(3), and depletion between them. Many mechanisms for the formation of compartments have been proposed, such as attraction of heterochromatin to the nuclear lamina(2,4), preferential attraction of similar chromatin to each other(1,4-12), higher levels of chromatin mobility in active chromatin(13-15) and transcription-related clustering of euchromatin(16,17). However, these hypotheses have remained inconclusive, owing to the difficulty of disentangling intra-chromatin and chromatin-lamina interactions in conventional nuclei(18). The marked reorganization of interphase chromosomes in the inverted nuclei of rods in nocturnal mammals(19,20) provides an opportunity to elucidate the mechanisms that underlie spatial compartmentalization. Here we combine Hi-C analysis of inverted  rod nuclei with microscopy and polymer simulations. We find that attractions between heterochromatic regions are crucial for establishing both compartmentalization and the concentric shells of pericentromeric heterochromatin, facultative heterochromatin and euchromatin in the inverted nucleus. When interactions between heterochromatin and the lamina are added, the  same model recreates the conventional nuclear organization. In addition, our models allow us to rule out mechanisms of compartmentalization that involve strong euchromatin interactions. Together, our experiments and modelling suggest  that attractions between heterochromatic regions are essential for the phase separation of the active and inactive genome in inverted and conventional nuclei, whereas interactions of the chromatin with the lamina are necessary to build the  conventional architecture from these segregated phases.", "date_created": "2019-09-26T18:42:55.934729+00:00", "published_by": "External", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2020-02-05T22:13:37.188825+00:00"}, "date_published": "2019-06", "public_release": "2019-10-22", "schema_version": "2", "static_content": [{"content": {"title": "HiGlass Views of Conventional and Inverted Nuclei", "name": "6c351627-e6cc-4a71-83f7-494f7a568104", "@id": "/higlass-view-configs/6c351627-e6cc-4a71-83f7-494f7a568104/", "uuid": "6c351627-e6cc-4a71-83f7-494f7a568104", "status": "released", "@type": ["HiglassViewConfig", "UserContent", "Item"], "description": "Non-rod neurons (top left) and WT thymocytes (bottom left) are conventional nuclei, with euchromatin in the interior. Rods (top right) and Lbr-/- thymocytes (bottom right) have inverted nuclei, with heterochromatin in the interior and euchromatin on the exterior.", "lab": {"display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@id": "/labs/4dn-dcic-lab/", "status": "current", "@type": ["Lab", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "award": {"status": "current", "@type": ["Award", "Item"], "@id": "/awards/1U01CA200059-01/", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "filetype": "HiglassViewConfig", "display_title": "HiGlass Views of Conventional and Inverted Nuclei", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:higlass_displays"}], "project_release": "2019-10-22", "contributing_labs": [{"@type": ["Lab", "Item"], "display_title": "Leonid Mirny, MIT", "correspondence": [{"contact_email": "bGVvbmlkQG1pdC5lZHU=", "@id": "/users/f520d12a-e4c4-4774-a230-08d6dc4f5ef1/", "display_title": "Leonid Mirny"}], "@id": "/labs/leonid-mirny-lab/", "uuid": "82ebab19-8a20-47c5-baeb-9a08a9524b10", "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.82ebab19-8a20-47c5-baeb-9a08a9524b10"]}}], "exp_sets_prod_in_pub": [{"uuid": "f66206f8-d0bb-49cf-be21-fee4a6d9b62f", "display_title": "4DNESX6A3WDX", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "@id": "/experiment-set-replicates/4DNESX6A3WDX/", "experimentset_type": "replicate", "accession": "4DNESX6A3WDX", "experiments_in_set": [{"uuid": "ff6fd7f4-a9d5-4ab5-b0a3-17dc1d0b7734", "display_title": "Dilution Hi-C on thymocyte with HindIII - 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