{"ID": "PMID:32213324", "aka": "https://www.biorxiv.org/content/10.1101/639922v1", "lab": {"@id": "/labs/oliver-rando-lab/", "title": "Oliver Rando, UMMS", "uuid": "60479b76-821b-4c03-b0e2-c9351291b965", "status": "current", "@type": ["Lab", "Item"], "correspondence": [{"contact_email": "b2xpdmVyLnJhbmRvQHVtYXNzbWVkLmVkdQ==", "@id": "/users/a42aa62c-9175-4dae-9319-4dc1ad6dac0a/", "display_title": "Oliver Rando"}], "display_title": "Oliver Rando, UMMS", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.60479b76-821b-4c03-b0e2-c9351291b965"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/32213324", "award": {"project": "4DN", "name": "1U54DK107980-01", "description": "NOFIC: The spatial organization of the genome impinges on all genomic processes, including gene regulation, maintenance of genome stability and chromosome transmission to daughter cells. A detailed understanding of the spatial arrangement of the human genome, referred to as the 4D nucleome, and the biological and physical principles that drive chromosome folding requires combining approaches from the fields of molecular and cell biology, imaging, genetics and genomics with approaches from physics, computational biology, and computer simulation. We have assembled a highly interdisciplinary center with the goal of generating extensively validated maps of the 4D nucleome, its physical and dynamic properties and its role in regulating the activity of the genome. First, the center will further optimize and extensively validate a suite of genome-wide molecular methodologies, based on chromosome conformation capture (3C) that can probe the folding of chromosomes at the scale of single nucleosomes, chromatin fibers, chromosomes and the entire nucleus, across cell populations and in single cells. Given that chromosome and nuclear organization is tightly linked to biological state of the cell, the center will map the 4D nucleome for four key biological states representing different conformations during the cell cycle (interphase and mitosis), and during cell differentiation (pluripotent and differentiated states). We will obtain complementary data regarding the structure and dynamics of chromatin, at different length scales and in single cells using extensive high-throughput imaging, live cell imaging and super resolution microscopy. Data obtained with all approaches will be analyzed, integrated and modeled using a set of methods we will further develop to gain insights into the structure, physics and dynamics of chromosome folding over different length scales. Finally, a critical component of our proposal is the biological validation and further elaboration of the chromatin interaction maps that are generated from our conformational analyses. This validation will be achieved through site-specific editing of genomic sequence and epigenetic marks, the creation of new contact points within the genome, and the identification of factors (both protein and nucleic acid) that facilitat or restrict these interactions. Effects of such perturbations in the chromosome conformation on transcription will reveal relationships between specific chromosome structural features and gene expression.", "@type": ["Award", "Item"], "center_title": "NOFIC - Dekker", "@id": "/awards/1U54DK107980-01/", "uuid": "ae6c618f-7a8c-441e-a886-e30bbbe591da", "status": "current", "display_title": "CENTER FOR 3D STRUCTURE AND PHYSICS OF THE GENOME", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Ultrastructural Details of Mammalian Chromosome Architecture.", "status": "current", "authors": ["Krietenstein N", "Abraham S", "Venev SV", "Abdennur N", "Gibcus J", "Hsieh TS", "Parsi KM", "Yang L", "Maehr R", "Mirny LA", "Dekker J", "Rando OJ"], "journal": "Molecular cell", "abstract": "Over the past decade, 3C-related methods have provided remarkable insights into chromosome folding in vivo. To overcome the limited resolution of prior studies,  we extend a recently developed Hi-C variant, Micro-C, to map chromosome architecture at nucleosome resolution in human ESCs and fibroblasts. Micro-C robustly captures known features of chromosome folding including compartment organization, topologically associating domains, and interactions between CTCF binding sites. In addition, Micro-C provides a detailed map of nucleosome positions and localizes contact domain boundaries with nucleosomal precision. Compared to Hi-C, Micro-C exhibits an order of magnitude greater dynamic range, allowing the identification of approximately 20,000 additional loops in each cell type. Many newly identified peaks are localized along extrusion stripes and form  transitive grids, consistent with their anchors being pause sites impeding cohesin-dependent loop extrusion. Our analyses comprise the highest-resolution maps of chromosome folding in human cells to date, providing a valuable resource  for studies of chromosome organization.", "date_created": "2020-03-30T15:23:00.892572+00:00", "published_by": "4DN", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2020-09-18T14:50:09.993540+00:00"}, "date_published": "2020-05-07", "public_release": "2020-03-30", "schema_version": "2", "static_content": [{"content": {"status": "released", "content": "Micro-C maps of H1 hESCs and HFFs tend to look very similar at mid-level resolutions, but at higher resolutions, close to nucleosome-level, Micro-C has a much higher signal-to-noise ratio. Below are comparisons of Micro-C and Hi-C in both cell types, first at 5kb resolution and below that at 50kb resolution.", "options": {"filetype": "md", "collapsible": false, "default_open": true}, "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "50035c3f-efc5-474b-af3a-7aeebb95b6e1", "display_title": "krietenstein.higlass-top", "@id": "/static-sections/50035c3f-efc5-474b-af3a-7aeebb95b6e1/", "name": "krietenstein.higlass-top", "@type": ["StaticSection", "UserContent", "Item"], "lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "content_as_html": "<div class=\"markdown-container\"><p>Micro-C maps of H1 hESCs and HFFs tend to look very similar at mid-level resolutions, but at higher resolutions, close to nucleosome-level, Micro-C has a much higher signal-to-noise ratio. Below are comparisons of Micro-C and Hi-C in both cell types, first at 5kb resolution and below that at 50kb resolution.</p></div>", "filetype": "md", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:higlass_displays"}, {"content": {"status": "released", "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "233a6636-f0d4-4677-9503-c58f95b14b6f", "display_title": "Micro-C vs Hi-C in H1-hESCs : 5kb resolution", "@id": "/higlass-view-configs/233a6636-f0d4-4677-9503-c58f95b14b6f/", "name": "233a6636-f0d4-4677-9503-c58f95b14b6f", "@type": ["HiglassViewConfig", "UserContent", "Item"], "lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "filetype": "HiglassViewConfig", "title": "Micro-C vs Hi-C in H1-hESCs : 5kb resolution", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:higlass_displays"}, {"content": {"status": "released", "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "8ad913a9-e863-4c3a-96f7-552c41f610c0", "display_title": "Micro-C vs Hi-C in HFFs: 5kb resolution", "@id": "/higlass-view-configs/8ad913a9-e863-4c3a-96f7-552c41f610c0/", "name": "8ad913a9-e863-4c3a-96f7-552c41f610c0", "@type": ["HiglassViewConfig", "UserContent", "Item"], "lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "filetype": "HiglassViewConfig", "title": "Micro-C vs Hi-C in HFFs: 5kb resolution", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:higlass_displays"}, {"content": {"status": "released", "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "cb019351-7186-4793-9475-d7c61a00b0d2", "display_title": "Micro-C vs Hi-C in H1-hESCs : 50kb resolution", "@id": "/higlass-view-configs/cb019351-7186-4793-9475-d7c61a00b0d2/", "name": "cb019351-7186-4793-9475-d7c61a00b0d2", "@type": ["HiglassViewConfig", "UserContent", "Item"], "lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "filetype": "HiglassViewConfig", "title": "Micro-C vs Hi-C in H1-hESCs : 50kb resolution", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:higlass_displays"}, {"content": {"status": "released", "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "0315a537-03ab-43f7-ae9e-970f0dfbd4d0", "display_title": "Micro-C vs Hi-C in HFFs: 50kb resolution", "@id": "/higlass-view-configs/0315a537-03ab-43f7-ae9e-970f0dfbd4d0/", "name": "0315a537-03ab-43f7-ae9e-970f0dfbd4d0", "@type": ["HiglassViewConfig", "UserContent", "Item"], "lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "filetype": "HiglassViewConfig", "title": "Micro-C vs Hi-C in HFFs: 50kb resolution", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:higlass_displays"}, {"content": {"status": "released", "content": "The Micro-C and Hi-C datasets produced in this publication \ncomprise some of the deepest Hi-C datasets on the 4DN portal \n(in terms of read depth). The HFFc6 Micro-C experiment set \n[4DNESWST3UBH](https://data.4dnucleome.org/experiment-set-replicates/4DNESWST3UBH/)\n is the deepest of all the 4DN data, with 5.86 billion read \npairs. \n\n-------------\n\n<br/>\n\n#### HiGlass Displays\n\nMicro-C maps of H1 hESCs and HFFs tend to look very similar at \nmid-level resolutions, but at higher resolutions, close to \nnucleosome-level, Micro-C has a much higher signal-to-noise \nratio. Below are comparisons of Micro-C and Hi-C in both cell \ntypes, first at 5kb resolution and below that at 50kb \nresolution.\n", "options": {"filetype": "md", "collapsible": false, "default_open": true}, "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "7a2b98bd-0a1e-49fb-86bc-3c0db18861ec", "display_title": "Curator's Note", "@id": "/static-sections/7a2b98bd-0a1e-49fb-86bc-3c0db18861ec/", "name": "krietenstein.overview-1", "@type": ["StaticSection", "UserContent", "Item"], "lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "content_as_html": "<div class=\"markdown-container\"><p>The Micro-C and Hi-C datasets produced in this publication \ncomprise some of the deepest Hi-C datasets on the 4DN portal \n(in terms of read depth). The HFFc6 Micro-C experiment set \n<a href=\"https://data.4dnucleome.org/experiment-set-replicates/4DNESWST3UBH/\" rel=\"noopener noreferrer\" target=\"_blank\">4DNESWST3UBH</a>\n is the deepest of all the 4DN data, with 5.86 billion read \npairs. </p>\n<hr/>\n<p><br/></p>\n<h4>HiGlass Displays</h4>\n<p>Micro-C maps of H1 hESCs and HFFs tend to look very similar at \nmid-level resolutions, but at higher resolutions, close to \nnucleosome-level, Micro-C has a much higher signal-to-noise \nratio. Below are comparisons of Micro-C and Hi-C in both cell \ntypes, first at 5kb resolution and below that at 50kb \nresolution.</p></div>", "filetype": "md", "title": "Curator's Note", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:overview"}, {"content": {"status": "released", "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - PHASE I", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "233a6636-f0d4-4677-9503-c58f95b14b6f", "display_title": "Micro-C vs Hi-C in H1-hESCs : 5kb resolution", "@id": "/higlass-view-configs/233a6636-f0d4-4677-9503-c58f95b14b6f/", "name": "233a6636-f0d4-4677-9503-c58f95b14b6f", "@type": ["HiglassViewConfig", "UserContent", "Item"], "lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "filetype": "HiglassViewConfig", "title": "Micro-C vs Hi-C in H1-hESCs : 5kb resolution", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:overview"}, {"content": {"status": "released", "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - 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PHASE I", "status": "current", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "uuid": "cb019351-7186-4793-9475-d7c61a00b0d2", "display_title": "Micro-C vs Hi-C in H1-hESCs : 50kb resolution", "@id": "/higlass-view-configs/cb019351-7186-4793-9475-d7c61a00b0d2/", "name": "cb019351-7186-4793-9475-d7c61a00b0d2", "@type": ["HiglassViewConfig", "UserContent", "Item"], "lab": {"status": "current", "display_title": "4DN DCIC, HMS", "uuid": "828cd4fe-ebb0-4b36-a94a-d2e3a36cc989", "@type": ["Lab", "Item"], "@id": "/labs/4dn-dcic-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.828cd4fe-ebb0-4b36-a94a-d2e3a36cc989"]}}, "filetype": "HiglassViewConfig", "title": "Micro-C vs Hi-C in H1-hESCs : 50kb resolution", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.owner", "userid.e2324f87-0625-4bbc-803b-d47677aebe08"]}}, "location": "tab:overview"}, {"content": {"status": "released", "award": {"@id": "/awards/1U01CA200059-01/", "uuid": "b0b9c607-f8b4-4f02-93f4-9895b461334b", "@type": ["Award", "Item"], "display_title": "4D NUCLEOME NETWORK DATA COORDINATION AND INTEGRATION CENTER - 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