{"lab": {"display_title": "Bing Ren, UCSD", "status": "current", "correspondence": [{"contact_email": "YmlyZW5AdWNzZC5lZHU=", "@id": "/users/e3159ffc-a5a9-43a1-8cfa-90b776c39788/", "display_title": "Bing Ren"}], "@id": "/labs/bing-ren-lab/", "title": "Bing Ren, UCSD", "uuid": "795847de-20b6-4f8c-ba8d-185215469cbf", "@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": {"project": "4DN", "center_title": "NOFIC - Ren", "description": "NOFIC: The complete sequencing of the human genome has provided an unprecedented opportunity for the study of the structure and function of the human genome. While our genome has historically been viewed as a linear sequence of bases, it has progressively become clear that this is an inadequate way to represent our genetic information. Notably, research over the last 30 years has begun to shed light on the fact that the higher-order, 3-dimensional organization of our genome plays a critical role in the interpretation of the genetic information encoded in our genome. The structure of our genome in the nucleus has been clearly demonstrated to play influential roles in diverse nuclear processes including DNA replication and gene expression. Despite this, our understanding of the structure of our genome within the nucleus remains incomplete. The reasons for this include limitations in the resolution and throughput of existing tools in chromatin topology mapping, a scarcity of the analytical tools for studying genome structure datasets, and the difficulty to relate the nuclear structure to function. Due to recent advancements in molecular methods based on high-throughput DNA sequencing, single cell analytical approaches, and high-resolution microscopy, the time for breaking through these previous limitations has come. We will establish a highly collaborative, innovative team in order to develop the tools necessary to transform our understanding of chromatin architecture and function in mammalian cells. We will begin by developing datasets that establish gold standards for the study of nuclear structure and function using genetic, biochemical and imaging approaches. We will optimize current existing technologies for mapping genome wide chromatin interactions, while also developing novel, complementary approaches for studying chromatin structure. We will also develop innovative analytical methods to interpret the chromatin structural data, unraveling principles of structural- and temporal- chromatin organization. Our highly collaborative team will draw on the diverse experiences of its members to provide a synergistic environment to push the limits of our understanding of nuclear structure. 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This duplication does not affect the higlass display of these files, howevver, downstream analyses using this file may encounter issues due to this pixel duplication.  The counts from the duplicate pixels can be aggregated to determine the correct count value at that location. If this issue is problematic for your needs you should consider regenerating the matrices from the merged pairs file of the associated dataset using a more recent version of cooler.  We are working to update the pipeline but do not yet have a predicted date for when this issue will be resolved."], "href": "/files-processed/4DNFIT5YVTLO/@@download/4DNFIT5YVTLO.mcool", "md5sum": "054ad55c51dd3612a7292913c60a89c3", "higlass_uid": "8a3c67fe-1b4c-4cdd-a8e1-c1876bf2ec6e", "file_classification": "processed file", "file_format": {"@type": ["FileFormat", "Item"], "display_title": "mcool", "uuid": "d13d06cf-218e-4f61-ccf0-91f226248b2c", "@id": "/file-formats/mcool/", "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "accession": "4DNFIT5YVTLO", "file_size": 8800546638, "uuid": "e4b8b418-f2d9-4873-8fa7-64cfc205f91b", "display_title": "4DNFIT5YVTLO.mcool", "status": "released", "file_type_detailed": "contact matrix (mcool)", "@id": "/files-processed/4DNFIT5YVTLO/", "@type": ["FileProcessed", "File", "Item"], "open_data_url": 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(2019) PMID:31427791", "authors": ["Zhang Y", "Li T", "Preissl S", "Amaral ML", "Grinstein JD", "Farah EN", "Destici E", "Qiu Y", "Hu R", "Lee AY", "Chee S", "Ma K", "Ye Z", "Zhu Q", "Huang H", "Fang R", "Yu L", "Izpisua Belmonte JC", "Wu J", "Evans SM", "Chi NC", "Ren B"], "url": "https://www.ncbi.nlm.nih.gov/pubmed/31427791", "date_published": "2019-09", "@id": "/publications/1037111f-92d5-48a4-aaf3-9952a39920f2/", "short_attribution": "Zhang Y et al. (2019)", "abstract": "Chromatin architecture has been implicated in cell type-specific gene regulatory  programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and  reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD  boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture.", "@type": ["Publication", "Item"], "title": "Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.", "ID": "PMID:31427791", "status": "current", "journal": "Nature genetics", "uuid": "1037111f-92d5-48a4-aaf3-9952a39920f2", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [], "publications_of_set": [{"display_title": "Zhang Y et al. (2019) PMID:31427791", "date_published": "2019-09", "abstract": "Chromatin architecture has been implicated in cell type-specific gene regulatory  programs, yet how chromatin remodels during development remains to be fully elucidated. Here, by interrogating chromatin reorganization during human pluripotent stem cell (hPSC) differentiation, we discover a role for the primate-specific endogenous retrotransposon human endogenous retrovirus subfamily H (HERV-H) in creating topologically associating domains (TADs) in hPSCs. Deleting these HERV-H elements eliminates their corresponding TAD boundaries and  reduces the transcription of upstream genes, while de novo insertion of HERV-H elements can introduce new TAD boundaries. The ability of HERV-H to create TAD boundaries depends on high transcription, as transcriptional repression of HERV-H elements prevents the formation of boundaries. This ability is not limited to hPSCs, as these actively transcribed HERV-H elements and their corresponding TAD  boundaries also appear in pluripotent stem cells from other hominids but not in more distantly related species lacking HERV-H elements. Overall, our results provide direct evidence for retrotransposons in actively shaping cell type- and species-specific chromatin architecture.", "ID": "PMID:31427791", "status": "current", "title": "Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells.", "journal": "Nature genetics", "uuid": "1037111f-92d5-48a4-aaf3-9952a39920f2", "@id": "/publications/1037111f-92d5-48a4-aaf3-9952a39920f2/", "authors": ["Zhang Y", "Li T", "Preissl S", "Amaral ML", "Grinstein JD", "Farah EN", "Destici E", "Qiu Y", "Hu R", "Lee AY", "Chee S", "Ma K", "Ye Z", "Zhu Q", "Huang H", "Fang R", "Yu L", "Izpisua Belmonte JC", "Wu J", "Evans SM", "Chi NC", "Ren B"], "@type": ["Publication", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 2, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBS7XFSAOQ/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing doubling_number", "Biosample missing culture_duration", "Biosample missing morphology_image"], "badge": {"commendation": null, "warning": "Biosample Metadata Incomplete", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group."}}}, {"parent": "/biosamples/4DNBS9U6Z6JB/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing doubling_number", "Biosample missing culture_duration", "Biosample missing morphology_image"], "badge": {"commendation": null, "warning": "Biosample Metadata Incomplete", "uuid": "2b2cc7ff-b7a8-4138-9a6c-22884fc71690", "@id": "/badges/biosample-metadata-incomplete/", "badge_icon": "/static/img/badges/biosample-icon.svg", "description": "Biosample is missing metadata information required as part of the standards implemented by the 4DN Samples working group."}}}]}, "validation-errors": []}