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Here, we dissect the role for G1 phase topologically associating domains (TADs), subTADs, and loops in the activation of replication initiation zones (IZs). We identify twelve subtypes of self-interacting chromatin domains distinguished by their degree of nesting, the presence of corner dot structures indicative of loops, and their co-localization with A/B compartments. Early replicating IZs localize to boundaries of nested corner-dot TAD/subTADs anchored by high density arrays of co-occupied CTCF+cohesin binding sites with divergently oriented motifs. By contrast, late replicating IZs localize to weak TADs/subTAD boundaries devoid of corner dots and most often anchored by singlet CTCF+cohesin sites. Upon global knock-down of cohesin-mediated loops in G1, early wave focal IZs replicate later in S phase and convert to diffuse placement along the genome. Moreover, IZs in mid-late S phase are delayed to the final minutes before entry into G2 when cohesin-mediated dot-less boundaries are ablated. We also delete a specific loop anchor and observe a sharp local delay of an early wave IZ to replication in late S phase. Our data demonstrate that cohesin-mediated loops at genetically-encoded TAD/subTAD boundaries in G1 phase are an essential determinant of the precise genomic placement of human replication origins in S phase.", "title": "Cohesin-mediated loop anchors confine the location of human replication origins", "journal": "bioRxiv", "date_published": "2021-01-06", "@id": "/publications/70a029d4-9432-4ceb-bd11-ad3b30188501/", "authors": ["Emerson DJ", "Zhao PA", "Klein K", "Ge C", "Zhou L", "Sasaki T", "Yang L", "Venvev SV", "Gibcus JH", "Dekker J", "Gilbert DM", "Phillips-Cremins JE"], "short_attribution": "Emerson DJ et al. (2021)", "status": "current", "@type": ["Publication", "Item"], "ID": "doi:10.1101/2021.01.05.425437", "display_title": "Emerson DJ et al. (2021) doi:10.1101/2021.01.05.425437", "uuid": "70a029d4-9432-4ceb-bd11-ad3b30188501", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"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.", "title": "Systematic evaluation of chromosome conformation capture assays.", "journal": "Nature methods", "date_published": "2021-09-03", "@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"], "short_attribution": "Akgol Oksuz B et al. (2021)", "status": "current", "@type": ["Publication", "Item"], "ID": "PMID:34480151", "display_title": "Akgol Oksuz B et al. (2021) PMID:34480151", "uuid": "dfc530f1-82c0-4ddc-8f95-6f40417f87a0", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "experiment_categorizer": {"field": "Enzyme", "value": "DpnII", "combined": "Enzyme: DpnII"}, "experiment_summary": "in situ Hi-C on H1-hESC (Tier 1) with DpnII", "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSZHFK3JF/", "embedded_path": "biosample.badges", "item": {"messages": ["Biosample missing doubling_number"], "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": []}