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While our genome has historically been viewed as a linear sequence of bases, it has progressively become clear that this is an inadequate way to represent our genetic information. Notably, research over the last 30 years has begun to shed light on the fact that the higher-order, 3-dimensional organization of our genome plays a critical role in the interpretation of the genetic information encoded in our genome. The structure of our genome in the nucleus has been clearly demonstrated to play influential roles in diverse nuclear processes including DNA replication and gene expression. Despite this, our understanding of the structure of our genome within the nucleus remains incomplete. The reasons for this include limitations in the resolution and throughput of existing tools in chromatin topology mapping, a scarcity of the analytical tools for studying genome structure datasets, and the difficulty to relate the nuclear structure to function. Due to recent advancements in molecular methods based on high-throughput DNA sequencing, single cell analytical approaches, and high-resolution microscopy, the time for breaking through these previous limitations has come. We will establish a highly collaborative, innovative team in order to develop the tools necessary to transform our understanding of chromatin architecture and function in mammalian cells. We will begin by developing datasets that establish gold standards for the study of nuclear structure and function using genetic, biochemical and imaging approaches. We will optimize current existing technologies for mapping genome wide chromatin interactions, while also developing novel, complementary approaches for studying chromatin structure. We will also develop innovative analytical methods to interpret the chromatin structural data, unraveling principles of structural- and temporal- chromatin organization. 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Analysis - they include PC1, Directionality Index (DI), TAD, Stripe and Loop calls", "higlass_view_config": {"error": "no view permissions"}}], "@id": "/experiment-set-replicates/4DNESIF5UIQE/", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "uuid": "17e0a7a6-ded4-462c-bc1d-126116fcdb3b", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "4DNESIF5UIQE", "external_references": [], "pubs_using": [{"uuid": "d313c2a4-aab7-417a-b9b4-bcf5ec5cdbac", "status": "current", "@id": "/publications/d313c2a4-aab7-417a-b9b4-bcf5ec5cdbac/", "@type": ["Publication", "Item"], "display_title": "Calandrelli R et al. (2021) doi:10.1101/2021.06.10.447969", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "publications_of_set": [{"display_title": "Calandrelli R et al. (2021) doi:10.1101/2021.06.10.447969", "ID": "doi:10.1101/2021.06.10.447969", "authors": ["Calandrelli R", "Wen X", "Nguyen TC", "Chen C-J", "Qi Z", "Chen W", "Yan Z", "Wu W", "Zaleta-Rivera K", "Hu R", "Yu M", "Wang Y", "Ma J", "Ren B", "Zhong S"], "journal": "bioRxiv", "@id": "/publications/d313c2a4-aab7-417a-b9b4-bcf5ec5cdbac/", "status": "current", "@type": ["Publication", "Item"], "title": "Three-dimensional organization of chromatin associated RNAs and their role in chromatin architecture in human cells", "uuid": "d313c2a4-aab7-417a-b9b4-bcf5ec5cdbac", "abstract": "Chromatin-associated RNA (caRNA) is a vital component of the interphase nucleus; yet its distribution and role in the three-dimensional (3D) genome organization and function remain poorly understood. Here, we map caRNAs spatial distribution on the 3D genome in human embryonic stem cells, fibroblasts, and myelogenous leukemia cells. We find that the relative abundance of trans-acting caRNA reflects the functional nuclear compartmentalization of the 3D genome, and the caRNAs sequence features are predictive of its spatial localization. We observe extensive caRNA-genome interactions that span several hundred kilobases to several megabases. These caRNA domains correlate with chromatin loops and enhancer-promoter interactions. We report a tradeoff of caRNAs promotive and suppressive roles to chromatin interactions. As a result, caRNA promotes chromatin interactions outside the anchors of chromatin loops, whereas caRNA exhibits an overall suppressive impact to chromatin interactions between loop anchors. Furthermore, caRNA suppresses chromatin loops number and strengths genome-wide, and this suppression depends on electric charge-mediated RNA interactions. These results reveal caRNAs multifaced role in regulating 3D chromatin organization and highlight caRNAs ability to modulate chromatin looping.", "date_published": "2021-07-14", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "number_of_experiments": 2, "@context": "/terms/", "aggregated-items": {"badges": [{"parent": "/biosamples/4DNBSPZROVPF/", "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/4DNBSWRCYVPJ/", "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": []}