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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.", "@id": "/publications/a716e6b4-9cfa-4f8d-a2c7-cabf21d42b95/", "short_attribution": "Krietenstein N et al. (2020)", "@type": ["Publication", "Item"], "url": "https://www.ncbi.nlm.nih.gov/pubmed/32213324", "journal": "Molecular cell", "date_published": "2020-05-07", "uuid": "a716e6b4-9cfa-4f8d-a2c7-cabf21d42b95", "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"], "ID": "PMID:32213324", "display_title": "Krietenstein N et al. (2020) PMID:32213324", "title": "Ultrastructural Details of Mammalian Chromosome Architecture.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [{"status": "current", "display_title": "Akgol Oksuz B et al. (2021) PMID:34480151", "uuid": "dfc530f1-82c0-4ddc-8f95-6f40417f87a0", "@type": ["Publication", "Item"], "@id": "/publications/dfc530f1-82c0-4ddc-8f95-6f40417f87a0/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "publications_of_set": [{"title": "Ultrastructural Details of Mammalian Chromosome Architecture.", "uuid": "a716e6b4-9cfa-4f8d-a2c7-cabf21d42b95", "date_published": "2020-05-07", "status": "current", "@type": ["Publication", "Item"], "@id": "/publications/a716e6b4-9cfa-4f8d-a2c7-cabf21d42b95/", "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"], "display_title": "Krietenstein N et al. (2020) PMID:32213324", "ID": "PMID:32213324", "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.", "journal": "Molecular cell", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"title": "Systematic evaluation of chromosome conformation capture assays.", "uuid": "dfc530f1-82c0-4ddc-8f95-6f40417f87a0", "date_published": "2021-09", "status": "current", "@type": ["Publication", "Item"], "@id": "/publications/dfc530f1-82c0-4ddc-8f95-6f40417f87a0/", "authors": ["Akgol Oksuz B", "Yang L", "Abraham S", "Venev SV", "Krietenstein N", "Parsi KM", "Ozadam H", "Oomen ME", "Nand A", "Mao H", "Genga RMJ", "Maehr R", "Rando OJ", "Mirny LA", "Gibcus JH", "Dekker J"], "display_title": "Akgol Oksuz B et al. (2021) PMID:34480151", "ID": "PMID:34480151", "abstract": "Chromosome conformation capture (3C) assays are used to map chromatin interactions genome-wide. Chromatin interaction maps provide insights into the spatial organization of chromosomes and the mechanisms by which they fold. Hi-C and Micro-C are widely used 3C protocols that differ in key experimental parameters including cross-linking chemistry and chromatin fragmentation strategy. To understand how the choice of experimental protocol determines the ability to detect and quantify aspects of chromosome folding we have performed a systematic evaluation of 3C experimental parameters. We identified optimal protocol variants for either loop or compartment detection, optimizing fragment size and cross-linking chemistry. We used this knowledge to develop a greatly improved Hi-C protocol (Hi-C 3.0) that can detect both loops and compartments relatively effectively. In addition to providing benchmarked protocols, this work produced ultra-deep chromatin interaction maps using Micro-C, conventional Hi-C and Hi-C 3.0 for key cell lines used by the 4D Nucleome project.", "journal": "Nature methods", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 17, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSZOFFFM6/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample receives gold status for being a 4DN Tier 1 or Tier 2 cell line that follows the approved SOP and contains all of the pertinent metadata information as required by the 4DN Samples working group."], "badge": {"commendation": "Gold Biosample", "warning": null, "uuid": "6c2b7409-4478-4e15-aabc-1a0df6b883e9", "@id": "/badges/gold-biosample/", "badge_icon": "/static/img/badges/biosample-badge-gold-star.svg", "description": "Gold biosample"}}}, {"parent": "/biosamples/4DNBS7PAXQM7/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample receives gold status for being a 4DN Tier 1 or Tier 2 cell line that follows the approved SOP and contains all of the pertinent metadata information as required by the 4DN Samples working group."], "badge": {"commendation": "Gold Biosample", "warning": null, "uuid": "6c2b7409-4478-4e15-aabc-1a0df6b883e9", "@id": "/badges/gold-biosample/", "badge_icon": "/static/img/badges/biosample-badge-gold-star.svg", "description": "Gold biosample"}}}, {"parent": "/biosamples/4DNBSZP1XAA4/", "embedded_path": "experiments_in_set.biosample.badges", "item": {"messages": ["Biosample receives gold status for being a 4DN Tier 1 or Tier 2 cell line that follows the approved SOP and contains all of the pertinent metadata information as required by the 4DN Samples working group."], "badge": {"commendation": "Gold Biosample", "warning": null, "uuid": "6c2b7409-4478-4e15-aabc-1a0df6b883e9", "@id": "/badges/gold-biosample/", "badge_icon": "/static/img/badges/biosample-badge-gold-star.svg", "description": "Gold biosample"}}}]}, "validation-errors": []}