{"lab": {"@id": "/labs/tomoko-yamada-lab/", "uuid": "4e87e04c-6a49-4a71-8240-5fdae2f04b24", "display_title": "Tomoko Yamada, NW", "@type": ["Lab", "Item"], "correspondence": [{"contact_email": "dG9tb2tvLnlhbWFkYUBub3J0aHdlc3Rlcm4uZWR1", "@id": "/users/3b5a8696-b152-4a12-bcf1-69186d6bb510/", "display_title": "Tomoko Yamada"}], "status": "current", "title": "Tomoko Yamada, NW", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.4e87e04c-6a49-4a71-8240-5fdae2f04b24"]}}, "award": {"description": "NI-OFHHD: The long-term goals of the proposed research are to elucidate mechanisms of three-dimensional genome architecture in the control of neuronal connectivity in the brain. It has recently been found that physiological stimuli including sensory experience or developmental signals remodel neuronal genome architecture in vivo. Strikingly, it's found that long-distance genome interactions massively increase in the developing cerebellum in mice. The discovery of these long-distance interactions formed between genes critical for neuronal differentiation unveils novel nuclear mechanisms by which genome architecture may play a role in the wiring of the brain. These findings raise fundamental questions on the mechanisms and biological functions of these interactions in the brain, which will be addressed in this grant. First, the organizing principles of long-distance genome interactions in the brain will be elucidated. Based on the in vivo findings, the hypothesis that long-distance genomic interactions are organized by specific epigenetic and transcriptional features will be tested. In addition, the study will also test the hypothesis that anchors of long-distance interactions assemble into higher-ordered subnuclear structures including nuclear speckles or Mediator condensates, which function as transcriptionally active hubs. Second, the projcet will define mechanisms by which long-distance interactions are formed in development. The BAF chromatin remodeling complex alters the genome environment to activate or repress transcription and is required for brain development in mice and humans, and its dysregulation results in human neurodevelopmental disorders, including Coffin\u2013Siris syndrome and autism. Based on our preliminary findings, the hypothesis that the BAF complex transiently inhibits formation of long-distance genome interactions in immature neurons of the developing brain will be tested. Following early development, the inhibition of the long-distance interactions might be relieved by the recruitment of specific sets of transcription factors that drive terminal neuron differentiation. This project will test the hypothesis that these transcription regulators, identified using DNA motif analyses, promote the formation of the long-distance genome interactions. Finally, this study will also test the hypothesis that the formation of long-distance genome interactions is necessary for the maturation of neurons in vivo, including making proper connections with their pre- and post-synaptic partners. The proposed research is significant as it will advance our understanding of the mechanisms regulating genome architecture to control neuronal differentiation in mammalian brain. Furthermore, these studies will provide an integrated view on how genome folding in the nucleus orchestrates the assembly of neural circuits underlying behavior.", "name": "1U01DA053691-01", "@type": ["Award", "Item"], "status": "current", "@id": "/awards/1U01DA053691-01/", "project": "4DN", "center_title": "Yamada", "uuid": "cf1cc388-e816-4061-b354-61bc4f8a23f8", "display_title": "MECHANISMS OF GENOME ORGANIZATION IN BRAIN DEVELOPMENT AND BEHAVIOR", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "study": "Perturbed cerebellar neuron time series", "status": "released", "aliases": ["yamada-lab:hi-c-mouse-cerebellar_granule-top2b_KD-FANS_IVEd8-dCas9_KRAB-pnd14"], "accession": "4DNESCDQ9OV3", "condition": "8 day old neurons - Tob2b KD", "description": "in situ Hi-C on cerebellar granule neurons with top2b sgRNA isolated using FANS at day 8 after in vivo electroporation from dCas9-KRAB mouse postnatal day 14", "study_group": "Disrupted or Atypical Cells", "date_created": "2024-02-27T17:25:36.755793+00:00", "submitted_by": {"error": "no view permissions"}, "dataset_label": "Hi-C on mouse cerebellar granule neurons", "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-03-29T16:46:01.919874+00:00"}, "public_release": "2025-01-29", "replicate_exps": [{"bio_rep_no": 1, "tec_rep_no": 1, "replicate_exp": {"uuid": "1b2b752b-684c-4cfd-b7a1-1cfe9f543c15", "display_title": "in situ Hi-C on cerebellar granule neuron - 8 days old with MboI - 4DNEX587CS3U", "accession": "4DNEX587CS3U", "@id": "/experiments-hi-c/4DNEX587CS3U/", "status": "released", "@type": ["ExperimentHiC", "Experiment", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 1, "replicate_exp": {"uuid": "08421f1c-e59d-475d-a1b9-1021c683c481", "display_title": "in situ Hi-C on cerebellar granule neuron - 8 days old with MboI - 4DNEX55QJJWY", "accession": "4DNEX55QJJWY", "@id": "/experiments-hi-c/4DNEX55QJJWY/", "status": "released", "@type": ["ExperimentHiC", "Experiment", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 3, "tec_rep_no": 1, "replicate_exp": {"uuid": "d1c1a836-8b91-4468-a5b7-571ede1540df", "display_title": "in situ Hi-C on cerebellar granule neuron - 8 days old with MboI - 4DNEXNU7IEUD", "accession": "4DNEXNU7IEUD", "@id": "/experiments-hi-c/4DNEXNU7IEUD/", "status": "released", "@type": ["ExperimentHiC", "Experiment", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "schema_version": "2", "static_content": [{"content": {"display_title": "4DNESCDQ9OV3 - Processed files", "title": "4DNESCDQ9OV3 - Processed files", "@type": ["HiglassViewConfig", "UserContent", "Item"], "award": {"@type": ["Award", "Item"], "uuid": "cf1cc388-e816-4061-b354-61bc4f8a23f8", "display_title": "MECHANISMS OF GENOME ORGANIZATION IN BRAIN DEVELOPMENT AND BEHAVIOR", "@id": "/awards/1U01DA053691-01/", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "description": "4DNESCDQ9OV3 (in situ Hi-C on cerebellar granule neurons with top2b sgRNA isolated using FANS at day 8 after in vivo electroporation from dCas9-KRAB mouse postnatal day 14): 4DNFIT9OF3IN, 4DNFIIUTXNN6, 4DNFIC4ONN6Y, 4DNFIBSODDPI", "filetype": "HiglassViewConfig", "uuid": "51fe2182-b13a-46f2-b406-e8525e1cc8c2", "contributing_labs": [], "lab": {"display_title": "Tomoko Yamada, NW", "@id": "/labs/tomoko-yamada-lab/", "status": "current", "@type": ["Lab", "Item"], "uuid": "4e87e04c-6a49-4a71-8240-5fdae2f04b24", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.4e87e04c-6a49-4a71-8240-5fdae2f04b24"]}}, "name": "51fe2182-b13a-46f2-b406-e8525e1cc8c2", "status": "released", "@id": "/higlass-view-configs/51fe2182-b13a-46f2-b406-e8525e1cc8c2/", "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": {"@id": "/labs/4dn-dcic-lab/", "@type": ["Lab", "Item"], "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": {"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"]}}, "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>"}, {"lab": {"@id": "/labs/4dn-dcic-lab/", "@type": ["Lab", "Item"], "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": "<b>In Situ Hi-C</b>\n\n<p>\n   In situ Hi-C is a method to detect and quantify the pairwise interactions between chromosome regions across the entire genome. It was developed in 2014 as an improvement over the dilution Hi-C method. Compared to standard dilution Hi-C, this technique reduces the frequency of random ligation because the ligation is performed <i>in situ</i> inside the nucleus, a constrained space, instead of in solution, where DNA fragments are floating freely. In addition, this protocol can be done more quickly in the lab and was the first to introduce the use of 4-cutter restriction enzymes as opposed to the previous 6-cutters, providing higher resolution.\n</p>\n<p>\nThe protocol involves cross-linking the cells with formaldehyde to form links between physically adjacent DNA regions. The cells are then permeabilized with their nuclei intact. A 4-cutter restriction enzyme is used to digest the chromatin into multiple DNA fragments. The resulting fragments are biotinylated by end filling of the fragments ends. The fragments are then ligated and the DNA is purified and sheared. The biotinylated fragments are pulled down from the solution with streptavidin beads and a library is constructed and sequenced. Analysis of the resulting paired-end short read sequences produces a matrix that shows the number of interactions between different DNA regions.\n</p>\n<p>\nSee <a href=\"https://www.sciencedirect.com/science/article/pii/S0092867414014974?via%3Dihub\">Rao et al., 2014</a> for more details.\n</p>\n\n<div>\n<img style=\"width: 600px;max-width:100%;\" src=\"https://s3.amazonaws.com/4dn-dcic-public/static-pages/InfoBoxes/IsHC_fig1.png\"/>\n  <br/><br/>\n  <em>Image source: Rao et al., 2014, Figure 1A</em>\n</div>", "name": "item-page-headers.ExperimentType.insituhic", "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"]}}, "title": "Assay Description", "status": "released", "aliases": ["4dn-dcic-lab:experiment_infobox_hic"], "options": {"filetype": "html", "collapsible": false, "default_open": false, "convert_ext_links": true}, "date_created": "2018-09-07T18:19:43.777198+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2023-11-09T14:48:01.220007+00:00"}, "schema_version": "2", "@id": "/static-sections/298554ad-20e2-4449-a752-ac190123dab7/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "298554ad-20e2-4449-a752-ac190123dab7", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.56c9c683-bb11-471b-b590-c656f7dc03c1"]}, "display_title": "Assay Description", "external_references": [], "content": "<b>In Situ Hi-C</b>\n\n<p>\n   In situ Hi-C is a method to detect and quantify the pairwise interactions between chromosome regions across the entire genome. It was developed in 2014 as an improvement over the dilution Hi-C method. Compared to standard dilution Hi-C, this technique reduces the frequency of random ligation because the ligation is performed <i>in situ</i> inside the nucleus, a constrained space, instead of in solution, where DNA fragments are floating freely. In addition, this protocol can be done more quickly in the lab and was the first to introduce the use of 4-cutter restriction enzymes as opposed to the previous 6-cutters, providing higher resolution.\n</p>\n<p>\nThe protocol involves cross-linking the cells with formaldehyde to form links between physically adjacent DNA regions. The cells are then permeabilized with their nuclei intact. A 4-cutter restriction enzyme is used to digest the chromatin into multiple DNA fragments. The resulting fragments are biotinylated by end filling of the fragments ends. The fragments are then ligated and the DNA is purified and sheared. The biotinylated fragments are pulled down from the solution with streptavidin beads and a library is constructed and sequenced. Analysis of the resulting paired-end short read sequences produces a matrix that shows the number of interactions between different DNA regions.\n</p>\n<p>\nSee <a href=\"https://www.sciencedirect.com/science/article/pii/S0092867414014974?via%3Dihub\">Rao et al., 2014</a> for more details.\n</p>\n\n<div>\n<img style=\"width: 600px;max-width:100%;\" src=\"https://s3.amazonaws.com/4dn-dcic-public/static-pages/InfoBoxes/IsHC_fig1.png\"/>\n  <br/><br/>\n  <em>Image source: Rao et al., 2014, Figure 1A</em>\n</div>", "filetype": "html", "content_as_html": "<div class=\"html-container\"><b>In Situ Hi-C</b>\n<p>\n   In situ Hi-C is a method to detect and quantify the pairwise interactions between chromosome regions across the entire genome. It was developed in 2014 as an improvement over the dilution Hi-C method. Compared to standard dilution Hi-C, this technique reduces the frequency of random ligation because the ligation is performed <i>in situ</i> inside the nucleus, a constrained space, instead of in solution, where DNA fragments are floating freely. In addition, this protocol can be done more quickly in the lab and was the first to introduce the use of 4-cutter restriction enzymes as opposed to the previous 6-cutters, providing higher resolution.\n</p>\n<p>\nThe protocol involves cross-linking the cells with formaldehyde to form links between physically adjacent DNA regions. The cells are then permeabilized with their nuclei intact. A 4-cutter restriction enzyme is used to digest the chromatin into multiple DNA fragments. The resulting fragments are biotinylated by end filling of the fragments ends. The fragments are then ligated and the DNA is purified and sheared. The biotinylated fragments are pulled down from the solution with streptavidin beads and a library is constructed and sequenced. Analysis of the resulting paired-end short read sequences produces a matrix that shows the number of interactions between different DNA regions.\n</p>\n<p>\nSee <a href=\"https://www.sciencedirect.com/science/article/pii/S0092867414014974?via%3Dihub\" rel=\"noopener noreferrer\" target=\"_blank\">Rao et al., 2014</a> for more details.\n</p>\n<div>\n<img src=\"https://s3.amazonaws.com/4dn-dcic-public/static-pages/InfoBoxes/IsHC_fig1.png\" style=\"width: 600px;max-width:100%;\"/>\n<br/><br/>\n<em>Image source: Rao et al., 2014, Figure 1A</em>\n</div></div>"}], "processed_files": [{"file_classification": "processed file", "upload_key": "c5884dc8-76b1-4181-a4b3-fd0157f961ad/4DNFICP87WUU.pairs.gz", "accession": "4DNFICP87WUU", "file_type": "contact list-combined", "file_type_detailed": "contact list-combined (pairs)", "uuid": "c5884dc8-76b1-4181-a4b3-fd0157f961ad", "md5sum": "142947b979d28ab256219194f2f9bf86", "file_size": 3582024700, "display_title": "4DNFICP87WUU.pairs.gz", "@id": 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