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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. Finally, there is an urgent need for high-throughput approaches that query the functional relevance of genome compartmentalization. For this Center grant, we propose to meet these needs through the following Aims: 1. Develop a strategy that connects microscopy views to genome-wide maps that, together with modeling, reveal the localization and dynamics of genomic regions relative to all major nuclear compartments. 2. Develop methods for efficient manipulation of the genome in order to elucidate mechanisms that target loci to specific compartments. 3. Develop methods to measure, model, and validate the functional relevance of nuclear compartments. The combined results of these approaches will reveal causal relationships now hidden among entangled genomic, epigenetic, and nuclear organization features. Deliverables of this proposal include a wide range of structural and functional maps of nuclear organization, reagents for visualizing endogenous chromosome loci, a powerful pipeline for synthesis of ~100kb DNA fragments, and cell lines facilitating repeated, high-fidelity insertio of these large fragments back into selected sites in the genome. These resources will provide a powerful complement to other 4D Nucleome Consortium efforts. A key strength of this Center proposal is the experience and complementary research capabilities of its five Investigators. 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Please direct any questions to the [Data Coordination and Integration Center](mailto:support@4dnucleome.org).", "name": "item-page-headers.ExperimentSet.data-usage-guidelines", "award": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "@id": "/awards/1U01CA200059-01/", "status": "current", "@type": ["Award", "Item"], "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Data Usage Guidelines", "status": "released", "aliases": [], "options": {"filetype": "md", "title_icon": "exclamation-circle", "collapsible": false, "default_open": true}, "date_created": "2018-08-06T03:09:55.543206+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2022-05-09T09:31:34.537494+00:00"}, "schema_version": "2", "@id": "/static-sections/621e8359-3885-40ce-965d-91894aa7b758/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "621e8359-3885-40ce-965d-91894aa7b758", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.986b362f-4eb6-4a9c-8173-3ab267228139"]}, "display_title": "Data Usage Guidelines", "external_references": [], "content": "\n**Data Use Guidelines:** This is a data set generated by the \n4DN Network and made freely available to the scientific \ncommunity. If you are intending to use these data for a \npublication, we ask that you please contact the data \ngenerating lab to discuss possible coordinated publication. \nIn your manuscript, please cite the 4DN White Paper \n([doi:10.1038/nature23884](https://doi.org/10.1038/nature23884)) \nand the 4DN Data Portal paper \n([doi:10.1038/s41467-022-29697-4](https://doi.org/10.1038/s41467-022-29697-4)), \nand please acknowledge the 4DN lab which generated the data. Please direct any questions to the [Data Coordination and Integration Center](mailto:support@4dnucleome.org).", "filetype": "md", "content_as_html": "

Data Use Guidelines: This is a data set generated by the \n4DN Network and made freely available to the scientific \ncommunity. If you are intending to use these data for a \npublication, we ask that you please contact the data \ngenerating lab to discuss possible coordinated publication. \nIn your manuscript, please cite the 4DN White Paper \n(doi:10.1038/nature23884) \nand the 4DN Data Portal paper \n(doi:10.1038/s41467-022-29697-4), \nand please acknowledge the 4DN lab which generated the data. Please direct any questions to the Data Coordination and Integration Center.

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(2024) PMID:39271748", "@type": ["Publication", "Item"], "ID": "PMID:39271748", "abstract": "Genome differential positioning within interphase nuclei remains poorly explored. We extended and validated Tyramide Signal Amplification (TSA)-seq to map genomic regions near nucleoli and pericentric heterochromatin in four human cell lines. Our study confirmed that smaller chromosomes localize closer to nucleoli but further deconvolved this by revealing a preference for chromosome arms below 36-46 Mbp in length. We identified two lamina associated domain subsets through their differential nuclear lamina versus nucleolar positioning in different cell lines which showed distinctive patterns of DNA replication timing and gene expression across all cell lines. Unexpectedly, active, nuclear speckle-associated genomic regions were found near typically repressive nuclear compartments, which is attributable to the close proximity of nuclear speckles and nucleoli in some cell types, and association of centromeres with nuclear speckles in human embryonic stem cells (hESCs). Our study points to a more complex and variable nuclear genome organization than suggested by current models, as revealed by our TSA-seq methodology.", "uuid": "22e02dc4-37b9-4891-9084-6d85f6683252", "journal": "Communications biology", "title": "Nucleolus and centromere Tyramide Signal Amplification-Seq reveals variable localization of heterochromatin in different cell types.", "@id": "/publications/22e02dc4-37b9-4891-9084-6d85f6683252/", "authors": ["Kumar P", "Gholamalamdari O", "Zhang Y", "Zhang L", "Vertii A", "van Schaik T", "Peric-Hupkes D", "Sasaki T", "Gilbert DM", "van Steensel B", "Ma J", "Kaufman PD", "Belmont AS"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"date_published": "2023-08", "status": "current", "display_title": "Buckberry S et al. (2023) PMID:37587336", "@type": ["Publication", "Item"], "ID": "PMID:37587336", "abstract": "Cells undergo a major epigenome reconfiguration when reprogrammed to human induced pluripotent stem cells (hiPS cells). However, the epigenomes of hiPS cells and human embryonic stem (hES) cells differ significantly, which affects hiPS cell function(1-8). These differences include epigenetic memory and aberrations that emerge during reprogramming, for which the mechanisms remain unknown. Here we characterized the persistence and emergence of these epigenetic differences by performing genome-wide DNA methylation profiling throughout primed and naive reprogramming of human somatic cells to hiPS cells. We found that reprogramming-induced epigenetic aberrations emerge midway through primed reprogramming, whereas DNA demethylation begins early in naive reprogramming. Using this knowledge, we developed a transient-naive-treatment (TNT) reprogramming strategy that emulates the embryonic epigenetic reset. We show that the epigenetic memory in hiPS cells is concentrated in cell of origin-dependent repressive chromatin marked by H3K9me3, lamin-B1 and aberrant CpH methylation. TNT reprogramming reconfigures these domains to a hES cell-like state and does not disrupt genomic imprinting. Using an isogenic system, we demonstrate that TNT reprogramming can correct the transposable element overexpression and differential gene expression seen in conventional hiPS cells, and that TNT-reprogrammed hiPS and hES cells show similar differentiation efficiencies. Moreover, TNT reprogramming enhances the differentiation of hiPS cells derived from multiple cell types. Thus, TNT reprogramming corrects epigenetic memory and aberrations, producing hiPS cells that are molecularly and functionally more similar to hES cells than conventional hiPS cells. We foresee TNT reprogramming becoming a new standard for biomedical and therapeutic applications and providing a novel system for studying epigenetic memory.", "uuid": "0d4af084-38e2-4a91-aa63-b170ffbe252b", "journal": "Nature", "title": "Transient naive reprogramming corrects hiPS cells functionally and epigenetically.", "@id": "/publications/0d4af084-38e2-4a91-aa63-b170ffbe252b/", "authors": ["Buckberry S", "Liu X", "Poppe D", "Tan JP", "Sun G", "Chen J", "Nguyen TV", "de Mendoza A", "Pflueger J", "Frazer T", "Vargas-Landin DB", "Paynter JM", "Smits N", "Liu N", "Ouyang JF", "Rossello FJ", "Chy HS", "Rackham OJL", "Laslett AL", "Breen J", "Faulkner GJ", "Nefzger CM", "Polo JM", "Lister R"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"date_published": "2025-02-26", "status": "current", "display_title": "Gholamalamdari O et al. (2025) PMID:38712201", "@type": ["Publication", "Item"], "ID": "PMID:38712201", "abstract": "Models of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Whereas gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.", "uuid": "f2b3b3fb-e9af-484d-abeb-fe4316ffdc1a", "journal": "bioRxiv : the preprint server for biology", "title": "Beyond A and B Compartments: how major nuclear locales define nuclear genome organization and function.", "@id": "/publications/f2b3b3fb-e9af-484d-abeb-fe4316ffdc1a/", "authors": ["Gholamalamdari O", "van Schaik T", "Wang Y", "Kumar P", "Zhang L", "Zhang Y", "Gonzalez GAH", "Vouzas AE", "Zhao PA", "Gilbert DM", "Ma J", "van Steensel B", "Belmont AS"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 2, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSR7TC87A/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample receives gold status for being a 4DN Tier 1 or Tier 2 cell line that follows the approved SOP and contains all of the pertinent metadata information as required by the 4DN Samples working group."], "badge": {"commendation": "Gold Biosample", "warning": null, "uuid": "6c2b7409-4478-4e15-aabc-1a0df6b883e9", "@id": "/badges/gold-biosample/", "badge_icon": "/static/img/badges/biosample-badge-gold-star.svg", "description": "Gold biosample"}}}, {"parent": "/biosamples/4DNBSTQ7LRR9/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample receives gold status for being a 4DN Tier 1 or Tier 2 cell line that follows the approved SOP and contains all of the pertinent metadata information as required by the 4DN Samples working group."], "badge": {"commendation": "Gold Biosample", "warning": null, "uuid": "6c2b7409-4478-4e15-aabc-1a0df6b883e9", "@id": "/badges/gold-biosample/", "badge_icon": "/static/img/badges/biosample-badge-gold-star.svg", "description": "Gold biosample"}}}]}, "validation-errors": []}