{"lab": {"uuid": "5771d772-1d10-43ea-bec1-0ea8c5a58503", "title": "Erez Lieberman Aiden, BCM", "@type": ["Lab", "Item"], "@id": "/labs/erez-liebermanaiden-lab/", "correspondence": [{"contact_email": "ZXJlekBlcmV6LmNvbQ==", "@id": "/users/60938b2e-e120-4c4f-9ddb-001296021df7/", "display_title": "Erez Lieberman Aiden"}], "display_title": "Erez Lieberman Aiden, BCM", "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.5771d772-1d10-43ea-bec1-0ea8c5a58503"]}}, "award": {"center_title": "Lieberman Aiden", "@id": "/awards/OD008540-01/", "status": "current", "@type": ["Award", "Item"], "project": "External", "display_title": "EXPLORING HOW THE GENOME FOLDS THROUGH PROXIMITY LIGATION AND SEQUENCING", "description": "Biological systems contain a large number of components whose physical interactions bring about cellular processes. A fundamental problem in molecular biology is to catalog these interactions and to decipher their functional consequences. High throughput sequencing has made it possible to characterize some of these interactions rapidly, at high-resolution, and in vivo (e.g., protein-DNA binding via ChIP-Seq and protein-RNA binding via RIP-Seq). But many interactions are not susceptible to these methods (e.g., RNA- RNA complexes, ncRNA-DNA binding, and - aside from recent work described below - DNA-DNA contacts and genome folding.) This gap may be bridged by coupling high-throughput sequencing with proximity-ligation-based methods. In proximity ligation, spatially proximate nucleic acids ligate to one another, forming a chimeric oligo. Observation of a chimera composed of X and Y suggests that X and Y must have been near one another in the original sample. As a result, questions about spatial arrangement become questions about sequence composition, making it possible to take advantage of high-throughput sequencing. Nevertheless, the development of these approaches is challenging: they involve subtle molecular biology and produce massive high-dimensional datasets requiring wholly new analytical paradigms including extensive physical modeling. We recently developed Hi-C, the first technology that couples proximity ligation and high-throughput sequencing in an unbiased, genome-wide fashion (Lieberman-Aiden et al., Science, 2009). Hi-C uses a DNA-DNA proximity ligation step to identify long-range physical contacts between genomic DNA loci in vivo. We used Hi-C to create a low-resolution three-dimensional map of the human genome, and made two significant discoveries: (1) genetic regulation is accompanied by the three-dimensional movement of genes from an 'on' compartment to an 'off' compartment, and vice-versa; (2) a never-before-seen macromolecular state, the fractal globule, which couples extraordinary spatial density and a total absence of knots. Here, we propose to dramatically extend the above work, by building a new generation of tools for systematically exploring the spatial organization of genomes, RNAs, and proteins, and by applying these tools to explore how RNAs and proteins establish and regulate the three-dimensional architecture of the genome. We will accomplish this through three specific research aims: (1) We will create an ensemble of new technologies combining proximity ligation and sequencing to enable comprehensive mapping of (a) DNA-RNA contacts [via DNA-RNA proximity ligation]; (b) RNA-RNA complexes [via RNA-RNA proximity ligation]; (c) selected protein-protein complexes [via probe-coupled proximity ligation]. We will use these methods to generate maps of biomolecular contacts in vivo. (2) We will create high-resolution Hi-C maps of mammalian genomes, comprehensively mapping promoter-enhancer contacts and exploring large-scale organizational features such as transcription factories. (3) We will develop new analytical approaches that combine the data produced by (1) and (2) with new (a) informatic tools, (b) computational analyses, (c) physical simulations, and (d) rigorous theoretical methods. We will characterize how physical interactions change during differentiation and tumorigenesis; identify the RNAs, proteins and pathways that that are most crucial in regulating genome folding, and produce detailed physical models of these pathways and how they modulate the physical structure of the genome. We plan to initially apply these techniques to characterize murine ES cells differentiating down a neural lineage, and later to differentiating human ES cells and to primary tumors. This effort will produce powerful new molecular methods which will dramatically improve our ability to assess the spatial arrangement of cellular components. It will transform our understanding of how mammalian genomes fold inside the nucleus. It will reveal how specific physical interactions between DNA, RNA, and protein play a role in differentiation, tumorigenesis, and genome folding, and suggest new drug targets in the process. Finally, this work will generate a series of datasets that will serve as valuable resources for the scientific community as a whole. Public Health Relevance: Biological systems contain a large number of components whose physical interactions bring about cellular processes, but our tools for identifying many of these biomolecular interactions are laborious and slow. We recently developed the Hi-C method for reconstructing the architecture of the human genome, and will extend this technological approach to map interactions between DNA, RNA, and protein in vivo and at high-throughput. We will use these maps to study how genome folding regulates cell function, and to characterize the process of cellular differentiation and tumorigenesis, identifying crucial biomolecular pathways and potential drug targets.", "name": "OD008540-01", "uuid": "36a06537-7831-494d-b10d-3e9fea931021", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "study": "Cohesin Protein Function", "status": "released", "aliases": ["4dn-dcic-lab:HCT-116_HCT-116-RAD21-mAC_in_situ_Hi-C_Rao-2017"], "dbxrefs": ["ENCODE:ENCSR123UVP"], "accession": "4DNES3QAGOZZ", "condition": "no auxin treatment", "description": "in situ Hi-C on HCT-116 (HCT-116-RAD21-mAC)", "study_group": "Disrupted or Atypical Cells", "date_created": "2019-05-15T15:09:05.933574+00:00", "submitted_by": {"error": "no view permissions"}, "dataset_label": "Hi-C on RAD21-AID tagged HCT-116", "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-07-09T06:46:02.746590+00:00"}, "public_release": "2019-11-26", "replicate_exps": [{"bio_rep_no": 1, "tec_rep_no": 1, "replicate_exp": {"@id": "/experiments-hi-c/4DNEXPEQRJJB/", "status": "released", "accession": "4DNEXPEQRJJB", "@type": ["ExperimentHiC", "Experiment", "Item"], "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 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4DNEXJP9KPSS", "uuid": "27ea0223-aa74-4cb4-a7b1-aaf01b70f4cf", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 2, "replicate_exp": {"@id": "/experiments-hi-c/4DNEXNTIZ7M9/", "status": "released", "accession": "4DNEXNTIZ7M9", "@type": ["ExperimentHiC", "Experiment", "Item"], "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 4DNEXNTIZ7M9", "uuid": "6e1496a1-2981-46b3-a19f-c19775a82aa2", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 3, "replicate_exp": {"@id": "/experiments-hi-c/4DNEXCXG4HJQ/", "status": "released", "accession": "4DNEXCXG4HJQ", "@type": ["ExperimentHiC", "Experiment", "Item"], "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 4DNEXCXG4HJQ", "uuid": "4d50c9c5-260e-4767-bdab-82c4620fd126", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 2, "tec_rep_no": 4, "replicate_exp": {"@id": "/experiments-hi-c/4DNEXPNLLZHH/", "status": "released", "accession": "4DNEXPNLLZHH", "@type": ["ExperimentHiC", "Experiment", "Item"], "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 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4DNEX2QIVOJX", "uuid": "560d11d2-e545-476c-a59b-3f792db51261", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 5, "tec_rep_no": 2, "replicate_exp": {"@id": "/experiments-hi-c/4DNEXYVYIVVY/", "status": "released", "accession": "4DNEXYVYIVVY", "@type": ["ExperimentHiC", "Experiment", "Item"], "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 4DNEXYVYIVVY", "uuid": "6fc35346-753a-4670-ab94-f7c44a680e54", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 6, "tec_rep_no": 1, "replicate_exp": {"@id": "/experiments-hi-c/4DNEX5GLIP2J/", "status": "released", "accession": "4DNEX5GLIP2J", "@type": ["ExperimentHiC", "Experiment", "Item"], "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 4DNEX5GLIP2J", "uuid": "3259d2da-e5bf-4206-b826-42efa9062504", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}, {"bio_rep_no": 6, "tec_rep_no": 2, "replicate_exp": {"@id": "/experiments-hi-c/4DNEX3OV1BPS/", "status": "released", "accession": "4DNEX3OV1BPS", "@type": ["ExperimentHiC", "Experiment", "Item"], "display_title": "in situ Hi-C on HCT116 with Crispr generated mClover and AID-tagged RAD21 with MboI - 4DNEX3OV1BPS", "uuid": "426f321b-0b08-433f-9a58-df8d758c0d5d", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}}], "schema_version": "2", "static_content": [{"content": {"@type": ["HiglassViewConfig", "UserContent", "Item"], "uuid": "6b08b61b-af27-4d28-844b-2c586aecec3a", "name": "6b08b61b-af27-4d28-844b-2c586aecec3a", "award": {"status": "current", "uuid": "36a06537-7831-494d-b10d-3e9fea931021", "@id": "/awards/OD008540-01/", "@type": ["Award", "Item"], "display_title": "EXPLORING HOW THE GENOME FOLDS THROUGH PROXIMITY LIGATION AND SEQUENCING", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "status": "released", "title": "4DNES3QAGOZZ - Processed files", "description": "4DNES3QAGOZZ (in situ Hi-C on HCT-116 (HCT-116-RAD21-mAC)): 4DNFIFLDVASC, 4DNFIBKY9EG9, 4DNFIGKFF445, 4DNFIZHT1Y8P", "filetype": "HiglassViewConfig", "display_title": "4DNES3QAGOZZ - Processed files", "@id": "/higlass-view-configs/6b08b61b-af27-4d28-844b-2c586aecec3a/", "lab": {"display_title": "Erez Lieberman Aiden, BCM", "uuid": "5771d772-1d10-43ea-bec1-0ea8c5a58503", "@id": "/labs/erez-liebermanaiden-lab/", "@type": ["Lab", "Item"], "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.5771d772-1d10-43ea-bec1-0ea8c5a58503"]}}, "contributing_labs": [], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.986b362f-4eb6-4a9c-8173-3ab267307e3a"]}}, "location": "tab:processed-files", "description": "auto_generated_higlass_view_config"}], "static_headers": [{"lab": {"@type": ["Lab", "Item"], "status": "current", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "display_title": "4DN DCIC, HMS", "@id": "/labs/4dn-dcic-lab/", "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": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "@id": "/awards/1U01CA200059-01/", "@type": ["Award", "Item"], "status": "current", "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>"}, {"lab": {"@type": ["Lab", "Item"], "status": "current", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "display_title": "4DN DCIC, HMS", "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "body": "Some annotated bam and pairs files generated in this Experiment Set may contain distinct reads that share the same identifier. This was caused by merging fastq files with integer identifiers (eg. @1, @2) during processing.", "name": "item-page-header.ES_files_with_integer_id_issue_warning_hic", "award": {"display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "@id": "/awards/1U01CA200059-01/", "@type": ["Award", "Item"], "status": "current", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Note on Processed Files", "status": "released", "aliases": ["4dn-dcic-lab:files_with_integer_id_issue_warning_hic_ES"], "options": {"filetype": "md", "collapsible": true, "default_open": true}, "date_created": "2020-04-06T19:36:49.278997+00:00", "section_type": "Item Page Header", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2020-04-19T23:58:37.106537+00:00"}, "schema_version": "2", "@id": "/static-sections/a16d9553-7158-4121-80f7-d1342213b3fa/", "@type": ["StaticSection", "UserContent", "Item"], "uuid": "a16d9553-7158-4121-80f7-d1342213b3fa", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.56c9c683-bb11-471b-b590-c656f7dc03c1"]}, "display_title": "Note on Processed Files", "external_references": [], "content": "Some annotated bam and pairs files generated in this Experiment Set may contain distinct reads that share the same identifier. This was caused by merging fastq files with integer identifiers (eg. @1, @2) during processing.", "filetype": "md", "content_as_html": "<div class=\"markdown-container\"><p>Some annotated bam and pairs files generated in this Experiment Set may contain distinct reads that share the same identifier. 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v0.3.0", "experiment_type": "in situ Hi-C", "assay_info": "MboI", "biosource_name": "HCT116 with Crispr generated mClover and AID-tagged RAD21", "lab_name": "4DN DCIC, HMS", "track_title": "contact matrix for HCT116 with Crispr generated mClover and AID-tagged RAD21 in situ Hi-C MboI"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "lab": {"name": "4dn-dcic-lab", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "last_modified": {"date_modified": "2025-02-20T19:46:49.776946+00:00"}}], "title": "HiC Processing Pipeline - v0.3.0", "description": "These are files generated using the updated Hi-C processing pipeline. They should be largely similar to those available in the Processed Files tab, which were generated with the previous version of the standard pipeline.  One potential difference of note is that the version of cooler used to generate the mcool file has a bug fix to prevent a pixel duplication issue which is observed in some files generated by the previous version of the pipeline.  Another notable difference is that a filter is applied to remove reads with MAPQ scores below 30 prior to mcool file generation.", "higlass_view_config": {"uuid": "56d240ef-e64f-4de8-ab23-08ce65d1ad5b", "description": "Supplementary Files (HiC Processing Pipeline - v0.3.0) for 4DNES3QAGOZZ (in situ Hi-C on HCT-116 (HCT-116-RAD21-mAC)): 4DNFID4T1I5S", "display_title": "4DNES3QAGOZZ - HiC Processing Pipeline - v0.3.0", "@id": "/higlass-view-configs/56d240ef-e64f-4de8-ab23-08ce65d1ad5b/", "@type": ["HiglassViewConfig", "UserContent", "Item"], "status": "released", "last_modified": {"date_modified": "2025-02-19T19:30:58.742630+00:00"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.7677f8a8-79d2-4cff-ab0a-a967a2a68e39"]}}}], "@id": "/experiment-set-replicates/4DNES3QAGOZZ/", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "uuid": "a60be947-aedf-47bf-9b46-5274e695003b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "4DNES3QAGOZZ", "external_references": [{"ref": "ENCODE:ENCSR123UVP", "uri": "https://www.encodeproject.org/ENCSR123UVP"}], "produced_in_pub": {"@type": ["Publication", "Item"], "uuid": "d45a47a9-4396-4782-87d1-ef9bf433755c", "title": "Cohesin Loss Eliminates All Loop Domains.", "journal": "Cell", "status": "current", "abstract": "The human genome folds to create thousands of intervals, called \"contact domains,\" that exhibit enhanced contact frequency within themselves. \"Loop domains\" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. \"Compartment domains\" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation  of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid.", "@id": "/publications/d45a47a9-4396-4782-87d1-ef9bf433755c/", "ID": "PMID:28985562", "date_published": "2017-10-05", "display_title": "Rao SSP et al. (2017) PMID:28985562", "authors": ["Rao SSP", "Huang SC", "Glenn St Hilaire B", "Engreitz JM", "Perez EM", "Kieffer-Kwon KR", "Sanborn AL", "Johnstone SE", "Bascom GD", "Bochkov ID", "Huang X", "Shamim MS", "Shin J", "Turner D", "Ye Z", "Omer AD", "Robinson JT", "Schlick T", "Bernstein BE", "Casellas R", "Lander ES", "Aiden EL"], "url": "https://www.ncbi.nlm.nih.gov/pubmed/28985562", "short_attribution": "Rao SSP et al. (2017)", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [{"uuid": "ee8db237-9a92-4b72-8292-a66028a95b5b", "display_title": "Emerson DJ et al. (2022) PMID:35676475", "@type": ["Publication", "Item"], "@id": "/publications/ee8db237-9a92-4b72-8292-a66028a95b5b/", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "publications_of_set": [{"@type": ["Publication", "Item"], "@id": "/publications/d45a47a9-4396-4782-87d1-ef9bf433755c/", "title": "Cohesin Loss Eliminates All Loop Domains.", "date_published": "2017-10-05", "status": "current", "ID": "PMID:28985562", "journal": "Cell", "display_title": "Rao SSP et al. (2017) PMID:28985562", "authors": ["Rao SSP", "Huang SC", "Glenn St Hilaire B", "Engreitz JM", "Perez EM", "Kieffer-Kwon KR", "Sanborn AL", "Johnstone SE", "Bascom GD", "Bochkov ID", "Huang X", "Shamim MS", "Shin J", "Turner D", "Ye Z", "Omer AD", "Robinson JT", "Schlick T", "Bernstein BE", "Casellas R", "Lander ES", "Aiden EL"], "uuid": "d45a47a9-4396-4782-87d1-ef9bf433755c", "abstract": "The human genome folds to create thousands of intervals, called \"contact domains,\" that exhibit enhanced contact frequency within themselves. \"Loop domains\" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. \"Compartment domains\" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation  of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@type": ["Publication", "Item"], "@id": "/publications/ee8db237-9a92-4b72-8292-a66028a95b5b/", "title": "Cohesin-mediated loop anchors confine the locations of human replication origins.", "date_published": "2022-06-08", "status": "current", "ID": "PMID:35676475", "journal": "Nature", "display_title": "Emerson DJ et al. (2022) PMID:35676475", "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"], "uuid": "ee8db237-9a92-4b72-8292-a66028a95b5b", "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.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 16, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSWF7O4HN/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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/4DNBSKR245XI/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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/4DNBSIUWQEXM/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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/4DNBSLJMVUY7/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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/4DNBS32O4BPD/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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/4DNBSYXCWN95/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample missing Cell Culture Details"], "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": []}