{"ID": "PMID:35676475", "aka": "http://biorxiv.org/lookup/doi/10.1101/2021.01.05.425437", "lab": {"title": "Jennifer Cremins, UPENN", "@type": ["Lab", "Item"], "@id": "/labs/jennifer-cremins-lab/", "uuid": "b18699f9-e3e9-44e2-8070-d5b044efc09e", "status": "current", "correspondence": [{"contact_email": "amNyZW1pbnNAc2Vhcy51cGVubi5lZHU=", "@id": "/users/8773d50c-1716-4153-9a18-d0f5ff2aa5ee/", "display_title": "Jennifer Phillips-Cremins"}], "display_title": "Jennifer Cremins, UPENN", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.b18699f9-e3e9-44e2-8070-d5b044efc09e"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/35676475", "award": {"center_title": "NT - Raj", "uuid": "cf0c686c-a3ad-411d-9986-ad42927352c0", "display_title": "ENGINEERING AND VISUALIZING GENOME FOLDING AT HIGH SPATIOTEMPORAL RESOLUTION", "description": "NT: Critical unanswered questions in the field of genome biology are how the dynamics of chromatin folding shape gene expression patterns. Our knowledge of the dynamics of higher-order 3-D folding of chromatin is severely limited, largely due to the lack of technologies to precisely image, engineer and monitor looping in a precise spatiotemporal manner across a population of cells. Here we propose to address these limitations by developing tools to dynamically alter chromatin folding in a synchronous manner across populations of cells as well as individual cells, and measure chromatin looping and its relationship to transcription at high spatial resolution in single cells. In Specific Aim 1 we will design tools to control looping dynamics. We will modify factors that fold chromatin at various levels, such as Ldb1 and CTCF by fusion to a moiety whose stability can be controlled by diffusible ligands. In combination with hi resolution 5C and single molecule imaging these tools are expected to generate fundamental insights into the relationship of nuclear architecture and gene expression mechanisms. In Specific Aim 2 we plan to engineer light-inducible systems for the precise control of looping dynamics. Using light activated dimerization domains that can be used in conjunction with designer DNA binding proteins we attempt to engineer factors used to rapidly promote or disrupt chromatin looping at various scales. This technology should enable studies not only in populations but also at the single cell level. In Specific Aim 3: we will develp reagents to study the transcriptional dynamics in relation to looping at the single cell level. We will combine RNA FISH with super-resolution imaging to develop a methodology for exploring the spatial and temporal structure of nascent transcription at high resolution. Combined with high-throughput image acquisition, we will discriminate the temporal dynamics of transcription by measuring the relative intensities arising from the different parts of the transcript. We will employ super-resolution imaging (STORM) to measure the spatial structure of transcription sites. These experiments are expected to reveal the impact of forced chromatin looping on distinct stages of the transcription cycle and elucidate the relationship between transcriptional burst kinetics and physical gene structure.", "@id": "/awards/1U01HL129998-01/", "status": "current", "@type": ["Award", "Item"], "name": "1U01HL129998-01", "project": "4DN", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Cohesin-mediated loop anchors confine the locations of human replication origins.", "status": "current", "authors": ["Emerson DJ", "Zhao PA", "Cook AL", "Barnett RJ", "Klein KN", "Saulebekova D", "Ge C", "Zhou L", "Simandi Z", "Minsk MK", "Titus KR", "Wang W", "Gong W", "Zhang D", "Yang L", "Venev SV", "Gibcus JH", "Yang H", "Sasaki T", "Kanemaki MT", "Yue F", "Dekker J", "Chen CL", "Gilbert DM", "Phillips-Cremins JE"], "journal": "Nature", "abstract": "DNA replication occurs through an intricately regulated series of molecular events and is fundamental for genome stability(1,2). At present, it is unknown how the locations of replication origins are determined in the human genome. Here we dissect the role of topologically associating domains (TADs)(3-6), subTADs(7)  and loops(8) in the positioning of replication initiation zones (IZs). We stratify TADs and subTADs by the presence of corner-dots indicative of loops and  the orientation of CTCF motifs. We find that high-efficiency, early replicating IZs localize to boundaries between adjacent corner-dot TADs anchored by high-density arrays of divergently and convergently oriented CTCF motifs. By contrast, low-efficiency IZs localize to weaker dotless boundaries. Following ablation of cohesin-mediated loop extrusion during G1, high-efficiency IZs become diffuse and delocalized at boundaries with complex CTCF motif orientations. Moreover, G1 knockdown of the cohesin unloading factor WAPL results in gained long-range loops and narrowed localization of IZs at the same boundaries. Finally, targeted deletion or insertion of specific boundaries causes local replication timing shifts consistent with IZ loss or gain, respectively. Our data support a model in which cohesin-mediated loop extrusion and stalling at a subset of genetically encoded TAD and subTAD boundaries is an essential determinant of the locations of replication origins in human S phase.", "categories": ["integrative analysis", "basic biology", "genomic annotations"], "date_created": "2022-06-09T13:48:38.481090+00:00", "published_by": "4DN", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2022-06-09T13:48:38.944465+00:00"}, "date_published": "2022-06-08", "public_release": "2022-06-09", "schema_version": "2", "static_content": [{"content": {"display_title": "Publication Status Update", "@id": "/static-sections/94f5d443-c509-435c-b4f9-06ac76d40fcd/", "options": {"filetype": "md", "collapsible": false, "default_open": true}, "@type": ["StaticSection", "UserContent", "Item"], "content": "Data presented here is that reported in this publication.  Previous versions of the data that were reported in the original biorxiv paper have been archived and are still available in the supplementary files tab on those datasets as indicated in the notes below.", "title": "Publication Status Update", "contributing_labs": [{"status": "current", "display_title": "David Gilbert, SDBRI", "@id": "/labs/david-gilbert-lab/", "uuid": "6423b207-8176-4f06-a127-951b98d6a53a", "@type": ["Lab", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.6423b207-8176-4f06-a127-951b98d6a53a"]}}], "content_as_html": "<div class=\"markdown-container\"><p>Data presented here is that reported in this publication.  Previous versions of the data that were reported in the original biorxiv paper have been archived and are still available in the supplementary files tab on those datasets as indicated in the notes below.</p></div>", "filetype": "md", "name": "emerson-etal.summary.temp_intro_blurb", "status": "released", "award": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE II", "status": "current", "@id": "/awards/2U01CA200059-06/", "uuid": "71171a4e-dca1-44cb-8375-fafd896c6923", "@type": ["Award", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "94f5d443-c509-435c-b4f9-06ac76d40fcd", "lab": {"uuid": "b18699f9-e3e9-44e2-8070-d5b044efc09e", "@id": "/labs/jennifer-cremins-lab/", "display_title": "Jennifer Cremins, UPENN", "@type": ["Lab", "Item"], "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.b18699f9-e3e9-44e2-8070-d5b044efc09e"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.986b362f-4eb6-4a9c-8173-3ab267227777"]}}, "location": "tab:data_summary"}, {"content": {"display_title": "5C Datasets", "@id": "/static-sections/ae5222b1-3758-40c8-8f37-2a968233ccb9/", "options": {"filetype": "jsx", "collapsible": false, "default_open": true}, "@type": ["StaticSection", "UserContent", "Item"], "content": "\n<EmbeddedItemSearchTable\n    searchHref=\"/search/?experiments_in_set.experiment_type.display_title=Capture+Hi-C&lab.display_title=Jennifer+Cremins%2C+UPENN&type=ExperimentSetReplicate&produced_in_pub.uuid=ee8db237-9a92-4b72-8292-a66028a95b5b\"\n    schemas={schemas}\n    session={session}\n    key=\"anyRandomTextString\"\n    facets={null}\n    columns={{\n        \"display_title\": {\n            \"title\": \"Title\"\n        },\n        \"experiments_in_set.experiment_type.display_title\" : {\n            \"title\" : \"Experiment Type\",\n        },\n        \"experiments_in_set.biosample.biosource_summary\": {\n            \"title\" : \"Biosample\"\n        },\n        \"experiments_in_set.biosample.modifications.display_title\": {\n            \"title\" : \"Modifications\"\n        },\n        \"experiments_in_set.experiment_categorizer.combined\" : {\n            \"title\" : \"Assay Details\"\n        }\n    }}\n/>\n", "title": "5C Datasets", "content_as_html": "<div class=\"html-container\">\n<EmbeddedItemSearchTable\n    searchHref=\"/search/?experiments_in_set.experiment_type.display_title=Capture+Hi-C&lab.display_title=Jennifer+Cremins%2C+UPENN&type=ExperimentSetReplicate&produced_in_pub.uuid=ee8db237-9a92-4b72-8292-a66028a95b5b\"\n    schemas={schemas}\n    session={session}\n    key=\"anyRandomTextString\"\n    facets={null}\n    columns={{\n        \"display_title\": {\n            \"title\": \"Title\"\n        },\n        \"experiments_in_set.experiment_type.display_title\" : {\n            \"title\" : \"Experiment Type\",\n        },\n        \"experiments_in_set.biosample.biosource_summary\": {\n            \"title\" : \"Biosample\"\n        },\n        \"experiments_in_set.biosample.modifications.display_title\": {\n            \"title\" : \"Modifications\"\n        },\n        \"experiments_in_set.experiment_categorizer.combined\" : {\n            \"title\" : \"Assay Details\"\n        }\n    }}\n/>\n</div>", "filetype": "jsx", "name": "emerson-etal.summary.5C-data-table", "status": "released", "award": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - 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PHASE II", "status": "current", "@id": "/awards/2U01CA200059-06/", "uuid": "71171a4e-dca1-44cb-8375-fafd896c6923", "@type": ["Award", "Item"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "d878de86-9b78-4f88-b5b5-802aba253ffc", "lab": {"uuid": "b18699f9-e3e9-44e2-8070-d5b044efc09e", "@id": "/labs/jennifer-cremins-lab/", "display_title": "Jennifer Cremins, UPENN", "@type": ["Lab", "Item"], "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.b18699f9-e3e9-44e2-8070-d5b044efc09e"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.986b362f-4eb6-4a9c-8173-3ab267227777"]}}, "location": "tab:data_summary"}, {"content": {"display_title": "Multi-fraction Repliseq Datasets", "@id": "/static-sections/bb4011d8-e7ac-48f4-bf09-f373e4a51340/", "options": {"filetype": "jsx", "collapsible": false, "default_open": true}, "@type": ["StaticSection", "UserContent", "Item"], "content": "<EmbeddedItemSearchTable\n    searchHref=\"/search/?type=ExperimentSet&accession=4DNES72NE7SL&accession=4DNES92AU9JR&accession=4DNESNGZM5FG&accession=4DNESXRBILXJ\"\n    schemas={schemas}\n    session={session}\n    key=\"anyRandomTextString\"\n    facets={null}\n    columns={{\n        \"display_title\": {\n            \"title\": \"Title\"\n        },\n        \"experiments_in_set.experiment_type.display_title\" : {\n            \"title\" : \"Experiment Type\",\n        },\n        \"experiments_in_set.biosample.biosource_summary\": {\n            \"title\" : \"Biosample\"\n        },\n        \"experiments_in_set.biosample.modifications.display_title\": {\n            \"title\" : \"Modifications\"\n        },\n        \"experiments_in_set.experiment_categorizer.combined\" : {\n            \"title\" : \"Assay Details\"\n        }\n    }}\n/>\n", "title": "Multi-fraction Repliseq Datasets", "content_as_html": "<div class=\"html-container\"><EmbeddedItemSearchTable\n    searchHref=\"/search/?type=ExperimentSet&accession=4DNES72NE7SL&accession=4DNES92AU9JR&accession=4DNESNGZM5FG&accession=4DNESXRBILXJ\"\n    schemas={schemas}\n    session={session}\n    key=\"anyRandomTextString\"\n    facets={null}\n    columns={{\n        \"display_title\": {\n            \"title\": \"Title\"\n        },\n        \"experiments_in_set.experiment_type.display_title\" : {\n            \"title\" : \"Experiment Type\",\n        },\n        \"experiments_in_set.biosample.biosource_summary\": {\n            \"title\" : \"Biosample\"\n        },\n        \"experiments_in_set.biosample.modifications.display_title\": {\n            \"title\" : \"Modifications\"\n        },\n        \"experiments_in_set.experiment_categorizer.combined\" : {\n            \"title\" : \"Assay Details\"\n        }\n    }}\n/>\n</div>", "filetype": "jsx", "name": "emerson-etal.summary.repliseq-data-table", "status": "released", "award": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - 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the previous calls can be found in the archived collection of supplementary files in <a href=\"https://data.4dnucleome.org/experiment-set-replicates/4DNES2M5JIGV/#supplementary-files\">4DNES2M5JIGV</a></p>\n\n<EmbeddedItemSearchTable\n    searchHref=\"/search/?type=FileProcessed&track_and_facet_info.experiment_bucket=TADs%2C+subTADs%2C+Boundaries%2C+and+Dot+Calls+-+Cremins+Lab&experiment_sets.accession=4DNESX75DD7R\"\n    schemas={schemas}\n    session={session}\n    key=\"anyRandomTextString\"\n    columns={{\n        \"display_title\": {\n            \"title\": \"Title\"\n        },\n        \"file_type\" : {\n            \"title\" : \"File Type\"\n        },\n        \"file_format.file_format\": {\n            \"title\" : \"File Format\"\n        },\n        \"file_size\" : {\n            \"title\" : \"File Size\"\n        }\n    }}\n    hideFacets={[\"lab.display_title\",\n                 \"track_and_facet_info.experiment_type\",\n                 \"track_and_facet_info.assay_info\",\n                 \"track_and_facet_info.biosource_name\",\n                 \"track_and_facet_info.lab_name\",\n                 \"public_release\",\n                 \"type\",\n                 \"status\",\n                 \"workflow_run_inputs.workflow.title\",\n                 \"workflow_run_outputs.workflow.title\",\n                 \"validation_errors.name\"\n                ]\n               }\n/>\n\n<H3>Feature Calls derived from <a href=\"https://data.4dnucleome.org/experiment-set-replicates/4DNES2R6PUEK/\">HFFc6 Hi-C - 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