{"lab": {"correspondence": [{"contact_email": "Yi52LnN0ZWVuc2VsQG5raS5ubA==", "@id": "/users/dd8b1cd6-93cd-41e5-b184-caf1369cb39f/", "display_title": "Bas van Steensel"}], "title": "Bas van Steensel, NKI", "status": "current", "@id": "/labs/bas-van-steensel-lab/", "display_title": "Bas van Steensel, NKI", "@type": ["Lab", "Item"], "uuid": "6343d57a-213e-4ac7-89ec-8b5e74c21bd2", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.6343d57a-213e-4ac7-89ec-8b5e74c21bd2"]}, "pi": {"error": "no view permissions"}}, "award": {"@type": ["Award", "Item"], "display_title": "COMBINED CYTOLOGICAL, GENOMIC, AND FUNCTIONAL MAPPING OF NUCLEAR GENOME ORGANIZATION", "uuid": "91b694c3-f4d7-4ddd-8278-16f94e15c1c5", "project": "4DN", "name": "1U54DK107965-01", "center_title": "NOFIC - Belmont", "@id": "/awards/1U54DK107965-01/", "description": "NOFIC: Decades of microscopy have revealed that the nucleus is not a homogeneous organelle, but rather consists of distinct compartments such as nucleoli, nuclear speckles, the nuclear lamina, among other structures. 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. Together they will pool their expertise for a concerted investigation into the biological functions of nuclear compartmentalization.", "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "status": "released", "aliases": ["vanSteensel-lab:HFF_4xAP3"], "accession": "4DNES9VPS41V", "condition": "Nucleolar Targeting Signal (4X-AP3)-Dam", "description": "DamID for Nucleolus (4X-AP3) on HFF wildtype cells - cells were transduced with virus expressing a Dam fusion protein, gDNA was harvested after 3 or 4 days and processed for DamID-seq", "date_created": "2020-07-01T07:53:56.805818+00:00", "submitted_by": {"error": "no view permissions"}, "dataset_label": "DamID-seq on HFFc6 cells (2020-07-01)", "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-02-22T18:46:54.288663+00:00"}, "public_release": "2023-11-03", "replicate_exps": [{"bio_rep_no": 1, "tec_rep_no": 1, "replicate_exp": {"display_title": "DamID-seq with DAM-Nucleolus on HFFc6 (Tier 1) - 4DNEX5J8T4V2", "@id": "/experiments-damid/4DNEX5J8T4V2/", "uuid": "8aebfe7f-a196-44bf-987b-a54b950f9d6e", "accession": "4DNEX5J8T4V2", "@type": ["ExperimentDamid", "Experiment", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 1, "replicate_exp": {"display_title": "DamID-seq with DAM-Nucleolus on HFFc6 (Tier 1) - 4DNEXGH34SZJ", "@id": "/experiments-damid/4DNEXGH34SZJ/", "uuid": "35bcf6a1-34a4-4621-b85b-99ca21ab7ab4", "accession": "4DNEXGH34SZJ", "@type": ["ExperimentDamid", "Experiment", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "schema_version": "2", "static_content": [{"content": {"@type": ["HiglassViewConfig", "UserContent", "Item"], "filetype": "HiglassViewConfig", "description": "4DNES9VPS41V (DamID for Nucleolus (4X-AP3) on HFF wildtype cells - cells were transduced with virus expressing a Dam fusion protein, gDNA was harvested after 3 or 4 days and processed for DamID-seq): 4DNFI78VB896, 4DNFIZKWSBLT, 4DNFI8G6UXCP, 4DNFIJGOMTGU, 4DNFIUJZM9JL, 4DNFI6V5XDEU", "display_title": "4DNES9VPS41V - Processed files", "status": "released", "lab": {"uuid": "6343d57a-213e-4ac7-89ec-8b5e74c21bd2", "@id": "/labs/bas-van-steensel-lab/", "display_title": "Bas van Steensel, NKI", "@type": ["Lab", "Item"], "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.6343d57a-213e-4ac7-89ec-8b5e74c21bd2"]}}, "@id": "/higlass-view-configs/f1d7fd45-026e-4338-801c-3986d8a79c80/", "uuid": "f1d7fd45-026e-4338-801c-3986d8a79c80", "name": "f1d7fd45-026e-4338-801c-3986d8a79c80", "award": {"uuid": "91b694c3-f4d7-4ddd-8278-16f94e15c1c5", "@type": ["Award", "Item"], "status": "current", "display_title": "COMBINED CYTOLOGICAL, GENOMIC, AND FUNCTIONAL MAPPING OF NUCLEAR GENOME ORGANIZATION", "@id": "/awards/1U54DK107965-01/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "4DNES9VPS41V - Processed files", "contributing_labs": [], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.7677f8a8-79d2-4cff-ab0a-a967a2a68e39"]}}, "location": "tab:processed-files", "description": "auto_generated_higlass_view_config"}], "static_headers": [{"lab": {"@type": ["Lab", "Item"], "@id": "/labs/bas-van-steensel-lab/", "display_title": "Bas van Steensel, NKI", "status": "current", "uuid": "6343d57a-213e-4ac7-89ec-8b5e74c21bd2", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.6343d57a-213e-4ac7-89ec-8b5e74c21bd2"]}}, "body": "Please use caution when using this data. Nucleolar DamID has not been validated extensively. Preliminary analyses suggest a substantial difference in data quality between cell lines. We interpret this as a difference in information content along the chromosomes due to more pronounced nucleolar interactions in some cell lines.", "name": "static-header.nucleolar_damid_caution", "award": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "@id": "/awards/1U01CA200059-01/", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Caution:", "status": "released", "aliases": ["4dn-dcic-lab:no_dam_id_seq_prelim_caution"], "options": {"filetype": "md", "collapsible": true, "default_open": true, "convert_ext_links": true}, "date_created": "2020-07-10T14:50:59.399365+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2023-11-03T14:45:16.647531+00:00"}, "schema_version": "2", "@id": "/static-sections/4dffb987-01e2-4747-866c-bafccbd014a3/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "4dffb987-01e2-4747-866c-bafccbd014a3", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.986b362f-4eb6-4a9c-8173-3ab267227777"]}, "display_title": "Caution:", "external_references": [], "content": "Please use caution when using this data. Nucleolar DamID has not been validated extensively. Preliminary analyses suggest a substantial difference in data quality between cell lines. We interpret this as a difference in information content along the chromosomes due to more pronounced nucleolar interactions in some cell lines.", "filetype": "md", "content_as_html": "<div class=\"markdown-container\"><p>Please use caution when using this data. Nucleolar DamID has not been validated extensively. Preliminary analyses suggest a substantial difference in data quality between cell lines. We interpret this as a difference in information content along the chromosomes due to more pronounced nucleolar interactions in some cell lines.</p></div>"}, {"lab": {"@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "display_title": "4DN DCIC, HMS", "status": "current", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "body": "\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).", "name": "item-page-headers.ExperimentSet.data-usage-guidelines", "award": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "@id": "/awards/1U01CA200059-01/", "status": "current", "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": "<div class=\"markdown-container\"><p><strong>Data Use Guidelines:</strong> 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(<a href=\"https://doi.org/10.1038/nature23884\" rel=\"noopener noreferrer\" target=\"_blank\">doi:10.1038/nature23884</a>) \nand the 4DN Data Portal paper \n(<a href=\"https://doi.org/10.1038/s41467-022-29697-4\" rel=\"noopener noreferrer\" target=\"_blank\">doi:10.1038/s41467-022-29697-4</a>), \nand please acknowledge the 4DN lab which generated the data. Please direct any questions to the <a href=\"mailto:support@4dnucleome.org\">Data Coordination and Integration Center</a>.</p></div>"}], "processed_files": [{"notes_to_tsv": ["This file contains processed results performed outside of the 4DN-DCIC standardized pipelines. 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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). 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