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Increasing evidence indicates that specific genomic regions each associate with these compartments. This genome compartmentalization has been linked to various functions, but these links are still poorly understood. Interestingly, Lamina Associated Domains (LADs) share specific heterochromatin marks, defining chromatin domains with distinct genetic and epigenetic properties. Genomic regions associating with other nuclear compartments may similarly define distinct classes of chromatin domains. One major bottleneck towards a deeper understanding of nuclear organization has been the inability to convert microscopy views of nuclear compartments into genome-wide maps that show which loci are associated with which compartment, and how the chromosomal fiber traverses between compartments. In addition, there is an urgent need for more efficient methods to dissect the mechanisms by which large genomic regions are targeted to specific nuclear compartments. 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(2019)", "ID": "PMID:30595451", "display_title": "Sima J et al. (2019) PMID:30595451", "date_published": "2019-02-07", "@type": ["Publication", "Item"], "@id": "/publications/015e1588-0290-44bf-a9f0-d4cad281c221/", "status": "current", "abstract": "The temporal order of DNA replication (replication timing [RT]) is highly coupled with genome architecture, but cis-elements regulating either remain elusive. We created a series of CRISPR-mediated deletions and inversions of a pluripotency-associated topologically associating domain (TAD) in mouse ESCs. CTCF-associated domain boundaries were dispensable for RT. CTCF protein depletion weakened most TAD boundaries but had no effect on RT or A/B compartmentalization  genome-wide. By contrast, deletion of three intra-TAD CTCF-independent 3D contact sites caused a domain-wide early-to-late RT shift, an A-to-B compartment switch,  weakening of TAD architecture, and loss of transcription. The dispensability of TAD boundaries and the necessity of these \"early replication control elements\" (ERCEs) was validated by deletions and inversions at additional domains. Our results demonstrate that discrete cis-regulatory elements orchestrate domain-wide RT, A/B compartmentalization, TAD architecture, and transcription, revealing fundamental principles linking genome structure and function.", "uuid": "015e1588-0290-44bf-a9f0-d4cad281c221", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"authors": ["Sima J", "Chakraborty A", "Dileep V", "Michalski M", "Klein KN", "Holcomb NP", "Turner JL", "Paulsen MT", "Rivera-Mulia JC", "Trevilla-Garcia C", "Bartlett DA", "Zhao PA", "Washburn BK", "Nora EP", "Kraft K", "Mundlos S", "Bruneau BG", "Ljungman M", "Fraser P", "Ay F", "Gilbert DM"], "@id": "/publications/015e1588-0290-44bf-a9f0-d4cad281c221/", "journal": "Cell", "ID": "PMID:30595451", "title": "Identifying cis Elements for Spatiotemporal Control of Mammalian DNA Replication.", "status": "current", "@type": ["Publication", "Item"], "display_title": "Sima J et al. (2019) PMID:30595451", "uuid": "015e1588-0290-44bf-a9f0-d4cad281c221", "date_published": "2019-02-07", "abstract": "The temporal order of DNA replication (replication timing [RT]) is highly coupled with genome architecture, but cis-elements regulating either remain elusive. We created a series of CRISPR-mediated deletions and inversions of a pluripotency-associated topologically associating domain (TAD) in mouse ESCs. CTCF-associated domain boundaries were dispensable for RT. CTCF protein depletion weakened most TAD boundaries but had no effect on RT or A/B compartmentalization  genome-wide. By contrast, deletion of three intra-TAD CTCF-independent 3D contact sites caused a domain-wide early-to-late RT shift, an A-to-B compartment switch,  weakening of TAD architecture, and loss of transcription. The dispensability of TAD boundaries and the necessity of these \"early replication control elements\" (ERCEs) was validated by deletions and inversions at additional domains. Our results demonstrate that discrete cis-regulatory elements orchestrate domain-wide RT, A/B compartmentalization, TAD architecture, and transcription, revealing fundamental principles linking genome structure and function.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 2, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSJG5ITLW/", "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/4DNBSX7OCKDX/", "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": []}