{"lab": {"@id": "/labs/bing-ren-lab/", "title": "Bing Ren, UCSD", "display_title": "Bing Ren, UCSD", "uuid": "795847de-20b6-4f8c-ba8d-185215469cbf", "correspondence": [{"contact_email": "YmlyZW5AdWNzZC5lZHU=", "@id": "/users/e3159ffc-a5a9-43a1-8cfa-90b776c39788/", "display_title": "Bing Ren"}], "status": "current", "@type": ["Lab", "Item"], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.795847de-20b6-4f8c-ba8d-185215469cbf"]}}, "award": {"description": "CDIMV: The transcriptional regulatory sequences communicate with each other dynamically in the 3D nuclear space to direct cell type specific gene expression. Currently, a major barrier to understanding the transcriptional regulatory programs is the lack of tools, models and maps to explore the chromatin architecture in diverse cell types and physiological contexts. We will address this pressing need by deploying transformative technologies to study the chromatin architecture in mammalian cells at an unprecedented resolution and scale. Specifically, we will generate navigable, cell-type-specific reference maps of chromatin architecture in the mouse, macaque and human brains by integrating high resolution and high throughput imaging and orthogonal single-cell-based genomic methods. We will also dissect the role of chromatin architecture in gene regulation through a set of controlled perturbation experiments in the mouse ES cells (ESC) and ESC-derived neural progenitor cells (NPC). We will develop structural models of chromatin organization with advanced polymer physics and statistical learning methods, and validate their predictive power in embryonic stem cells and in ex vivo brain slices. Finally, we will make the reference maps, analytical tools, visualization methods and structural models available to the broader community. The proposed research project will dramatically transform our ability to analyze the 4D Nucleome of complex tissues, and produce the much-needed maps, tools and models for understanding the gene regulatory programs encoded in the linear genome sequences.", "name": "1UM1HG011585-01", "@id": "/awards/1UM1HG011585-01/", "project": "4DN", "status": "current", "uuid": "ee89349a-1d43-4048-9142-bc750f0f3b32", "center_title": "CDIMV - Ren", "@type": ["Award", "Item"], "display_title": "CENTER FOR INTEGRATED MULTI-MODAL AND MULTI-SCALE NUCLEOME RESEARCH", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "badges": [{"badge": {"warning": "Replicate Numbers", "status": "released", "badge_icon": "/static/img/badges/replicates-orange-circle.svg", "display_title": "Replicate Numbers", "uuid": "24a64a84-3c33-4d76-aaf2-e5ef45eff347", "@id": "/badges/replicate-numbers/", "description": "Issues with replicate numbers", "badge_classification": "Warning", "@type": ["Badge", "Item"], "title": "Replicate Numbers", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "messages": ["Replicate set contains only a single biological replicate"]}], "status": "released", "aliases": ["bing-ren-lab:expset_dnafish_mouse_no-dtag_rad21"], "accession": "4DNESQD7KQVS", "condition": "FKBP12(F36V) degron targeting Rad21 (control)", "description": "Multiplexed FISH in Sox2 tagged mouse embryonic stem cell line (F123-CASTx129) with a 7.5kb insertion containing 4 CTCF binding sites introduced between Sox2 and its Super Enhancer.", "date_created": "2025-02-03T15:47:25.959778+00:00", "submitted_by": {"error": "no view permissions"}, "dataset_label": "Multiplexed FISH in Sox2 tagged F123-CASTx129 with 4CBS insertions between Sox2 and SE", "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-05-29T19:45:43.072037+00:00"}, "public_release": "2025-02-11", "replicate_exps": [{"bio_rep_no": 1, "tec_rep_no": 1, "replicate_exp": {"@id": "/experiments-mic/4DNEXYNSCQZP/", "status": "released", "@type": ["ExperimentMic", "Experiment", "Item"], "accession": "4DNEXYNSCQZP", "uuid": "4b14a35d-0da4-4c2f-9537-b2ee7ae935c0", "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEXYNSCQZP", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "schema_version": "2", "static_headers": [{"lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@id": "/labs/4dn-dcic-lab/", "@type": ["Lab", "Item"], "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": {"status": "current", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "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.

"}, {"lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@id": "/labs/4dn-dcic-lab/", "@type": ["Lab", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "body": "Processed files in this dataset are provided in the 4DN standard FISH-Omics Format - Chromatin Tracing (FOF-CT).\n\nThis is a collection of tabular files, consisting of several tables.\nThe DNA-spot/trace core table is organized around individual DNA bright Spots that are spatially linked together in a three-dimensional (3D) polymeric Trace.\nAdditional optional tables can complement this information and vary according to the specific dataset. \n\nThe full documentation is available here: https://fish-omics-format.readthedocs.io/", "name": "fof-ct.note", "award": {"status": "current", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE II", "@id": "/awards/2U01CA200059-06/", "uuid": "71171a4e-dca1-44cb-8375-fafd896c6923", "@type": ["Award", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Note on FOF-CT file format", "status": "released", "aliases": ["4dn-dcic-lab:fof_ct_note"], "options": {"filetype": "md", "collapsible": true, "default_open": false}, "date_created": "2022-03-07T18:23:27.469177+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2022-03-08T14:28:37.893086+00:00"}, "schema_version": "2", "@id": "/static-sections/a09a2833-b56b-4e81-8eff-bb8ae6aaa596/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "a09a2833-b56b-4e81-8eff-bb8ae6aaa596", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e4a22298-1da4-4e59-8a65-9e661f47fb48"]}, "display_title": "Note on FOF-CT file format", "external_references": [], "content": "Processed files in this dataset are provided in the 4DN standard FISH-Omics Format - Chromatin Tracing (FOF-CT).\n\nThis is a collection of tabular files, consisting of several tables.\nThe DNA-spot/trace core table is organized around individual DNA bright Spots that are spatially linked together in a three-dimensional (3D) polymeric Trace.\nAdditional optional tables can complement this information and vary according to the specific dataset. \n\nThe full documentation is available here: https://fish-omics-format.readthedocs.io/", "filetype": "md", "content_as_html": "

Processed files in this dataset are provided in the 4DN standard FISH-Omics Format - Chromatin Tracing (FOF-CT).

\n

This is a collection of tabular files, consisting of several tables.\nThe DNA-spot/trace core table is organized around individual DNA bright Spots that are spatially linked together in a three-dimensional (3D) polymeric Trace.\nAdditional optional tables can complement this information and vary according to the specific dataset.

\n

The full documentation is available here: https://fish-omics-format.readthedocs.io/

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(2025) PMID:40060486", "@type": ["Publication", "Item"], "authors": ["Tastemel M", "Jussila A", "Saravanan B", "Huang H", "Xie Y", "Zhu Q", "Jiang Y", "Armand E", "Ren B"], "@id": "/publications/7b338c4e-a510-41ff-b65a-389b1e270c97/", "uuid": "7b338c4e-a510-41ff-b65a-389b1e270c97", "date_published": "2025-02-26", "title": "Context-Dependent and Gene-Specific Role of Chromatin Architecture Mediated by Histone Modifiers and Loop-extrusion Machinery.", "journal": "bioRxiv : the preprint server for biology", "abstract": "Loop-extrusion machinery, comprising the cohesin complex and CCCTC-binding factor CTCF, organizes the interphase chromosomes into topologically associating domains (TADs) and loops, but acute depletion of components of this machinery results in variable transcriptional changes in different cell types, highlighting the complex relationship between chromatin organization and gene regulation. Here, we systematically investigated the role of 3D genome architecture in gene regulation in mouse embryonic stem cells under various perturbation conditions. We found that acute depletion of cohesin or CTCF disrupts the formation of TADs, but affects gene regulation in a gene-specific and context-dependent manner. Furthermore, the loop extrusion machinery was dispensable for transcription from most genes in steady state, consistent with prior results, but became critical for a large number of genes during transition of cellular states. Through a genome-wide CRISPR screen, we uncovered multiple factors that can modulate the role of loop extrusion machinery in gene regulation in a gene-specific manner. Among them were the MORF acetyltransferase complex members (Kat6b, Ing5, Brpf1), which could antagonize the transcriptional insulation mediated by CTCF and cohesin complex at developmental genes. Interestingly, inhibition of Kat6b partially rescues the insulator defects in cells lacking the cohesin loader Nipbl, mutations of which are responsible for the developmental disorder Cornelia de Lange syndrome. Taken together, our findings uncovered interplays between the loop extrusion machinery and histone modifying complex that underscore the context-dependent and gene-specific role of the 3D genome.", "ID": "PMID:40060486", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"journal": "bioRxiv : the preprint server for biology", "ID": "PMID:40060486", "status": "current", "abstract": "Loop-extrusion machinery, comprising the cohesin complex and CCCTC-binding factor CTCF, organizes the interphase chromosomes into topologically associating domains (TADs) and loops, but acute depletion of components of this machinery results in variable transcriptional changes in different cell types, highlighting the complex relationship between chromatin organization and gene regulation. Here, we systematically investigated the role of 3D genome architecture in gene regulation in mouse embryonic stem cells under various perturbation conditions. We found that acute depletion of cohesin or CTCF disrupts the formation of TADs, but affects gene regulation in a gene-specific and context-dependent manner. Furthermore, the loop extrusion machinery was dispensable for transcription from most genes in steady state, consistent with prior results, but became critical for a large number of genes during transition of cellular states. Through a genome-wide CRISPR screen, we uncovered multiple factors that can modulate the role of loop extrusion machinery in gene regulation in a gene-specific manner. Among them were the MORF acetyltransferase complex members (Kat6b, Ing5, Brpf1), which could antagonize the transcriptional insulation mediated by CTCF and cohesin complex at developmental genes. Interestingly, inhibition of Kat6b partially rescues the insulator defects in cells lacking the cohesin loader Nipbl, mutations of which are responsible for the developmental disorder Cornelia de Lange syndrome. Taken together, our findings uncovered interplays between the loop extrusion machinery and histone modifying complex that underscore the context-dependent and gene-specific role of the 3D genome.", "display_title": "Tastemel M et al. 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