{"lab": {"@type": ["Lab", "Item"], "@id": "/labs/paul-kaufman-lab/", "status": "current", "display_title": "Paul Kaufman, UMMS", "title": "Paul Kaufman, UMMS", "correspondence": [{"contact_email": "cGF1bGRrYXVmbWFuQGdtYWlsLmNvbQ==", "@id": "/users/73fbf532-ddec-4d87-8480-17ba5fb5edb7/", "display_title": "Paul Kaufman"}], "uuid": "feaabb54-cf04-4f85-8a03-44c1fcbbc1b0", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.feaabb54-cf04-4f85-8a03-44c1fcbbc1b0"]}}, "tags": ["4DN Joint Analysis 2018", "2018_01_internal", "2018_01_internal_JA"], "award": {"@type": ["Award", "Item"], "display_title": "NUCLEOLAR GENOMICS DURING EARLY MAMMALIAN DEVELOPMENT", "uuid": "54a81332-c7e2-4a3f-aff7-1f9f1d38dcd0", "name": "1U01DA040588-01", "center_title": "NBC - Kaufman", "status": "current", "project": "4DN", "@id": "/awards/1U01DA040588-01/", "description": "NBC: In all eukaryotes, the large ribosomal RNAs are transcribed from repeated ribosomal DNA (rDNA) genes. These rDNA repeats form nucleoli, which are specialized, non-membrane-bound sub-nuclear organelles that are the sites of ribosome assembly. Additionally, nucleoli are dynamic hubs through which numerous proteins shuttle. Less well investigated is the role of nucleoli in organizing the three dimensional structure of mammalian genomes. Long-range chromosome interactions are of great interest because they can regulate the developmental timing or the variegation of gene expression in mammalian cells. Deep sequencing analyses of DNA associated with isolated nucleoli from human somatic cell lines have shown that specific loci, termed nucleolar-associated domains (NADs), form frequent three-dimensional associations with nucleoli. NADs are dynamic, being redistributed to the nuclear periphery or to pericentric heterochromatin foci upon nucleolar alteration via inhibition of rDNA transcription. The human cell lines in which NADs have been studied to date are not suited for answering broad questions about the role of NADs in mammalian development. Early development is a critical period to study NAD biological function, not just because of the fundamental biological events that occur, but also because interactions between pericentromeric chromatin and perinucleolar regions are particularly dynamic during mammalian preimplantation embryonic development. We therefore propose that the biological importance of the 3D genome associations maintained by nucleoli should be explored in a system that allows analysis of mammalian developmental processes; that is, a system in which the functionality of these interactions can be explored in four dimensions. Therefore, we propose for the first time to map of the nucleolar-associated domains (NADs) in the mouse genome, determine how these associations are altered during embryonic stem cell (ESC) differentiation, and develop tools for study of these higher-order chromosome interaction in fixed and live single cells. In keeping with the goals of the NIH Initiative, we intend to produe databases and tools for understanding the 4D regulation of mammalian genome structure and function via NAD interactions, as a comprehensive foundation for the mammalian developmental biology community. Furthermore, we will determine how these associations are altered upon differentiation into each of the three germ layers, and how they are correlated with the global genome reorganization that occurs in post-implantation epiblasts. In addition to these population measurements, we will generate tools for the visualization of the repeat-rich DNAs associated with nucleoli in live, single cells via CRISPR-based targeting. In this manner, our project will be the first to analyze the dynamics of NAD-mediated genome organization during mammalian cell differentiation. 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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": {"@type": ["Award", "Item"], "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@id": "/awards/1U01CA200059-01/", "status": "current", "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "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. 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