{"lab": {"status": "current", "uuid": "3c577664-affb-41c4-bf27-9e21c2fc1554", "correspondence": [{"contact_email": "am9iLmRla2tlckB1bWFzc21lZC5lZHU=", "@id": "/users/83b5073a-069b-4162-9b30-6f42d5551e34/", "display_title": "Job Dekker"}], "@type": ["Lab", "Item"], "display_title": "Job Dekker, UMMS", "@id": "/labs/job-dekker-lab/", "title": "Job Dekker, UMMS", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.3c577664-affb-41c4-bf27-9e21c2fc1554"]}}, "tags": ["4DN Joint Analysis 2018", "2018_01_public", "2018_01_internal", "2018_01_internal_JA", "deep_data"], "award": {"name": "1U54DK107980-01", "status": "current", "@id": "/awards/1U54DK107980-01/", "display_title": "CENTER FOR 3D STRUCTURE AND PHYSICS OF THE GENOME", "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. 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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. 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(2020) PMID:32213324", "@type": ["Publication", "Item"], "short_attribution": "Krietenstein N et al. (2020)", "uuid": "a716e6b4-9cfa-4f8d-a2c7-cabf21d42b95", "status": "current", "date_published": "2020-05-07", "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.", "url": "https://www.ncbi.nlm.nih.gov/pubmed/32213324", "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"], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "pubs_using": [{"@type": ["Publication", "Item"], "uuid": "dfc530f1-82c0-4ddc-8f95-6f40417f87a0", "status": "current", "display_title": "Akgol Oksuz B et al. (2021) PMID:34480151", "@id": "/publications/dfc530f1-82c0-4ddc-8f95-6f40417f87a0/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"@type": ["Publication", "Item"], "uuid": "716f318f-490c-468e-828f-e7dff0fb7110", "status": "current", "display_title": "Dsouza KB et al. (2022) PMID:35764630", "@id": "/publications/716f318f-490c-468e-828f-e7dff0fb7110/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "publications_of_set": [{"status": "current", "uuid": "a716e6b4-9cfa-4f8d-a2c7-cabf21d42b95", "@type": ["Publication", "Item"], "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", "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": "/publications/a716e6b4-9cfa-4f8d-a2c7-cabf21d42b95/", "date_published": "2020-05-07", "display_title": "Krietenstein N et al. (2020) PMID:32213324", "title": "Ultrastructural Details of Mammalian Chromosome Architecture.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"status": "current", "uuid": "716f318f-490c-468e-828f-e7dff0fb7110", "@type": ["Publication", "Item"], "ID": "PMID:35764630", "abstract": "Despite the availability of chromatin conformation capture experiments,  discerning the relationship between the 1D genome and 3D conformation remains a  challenge, which limits our understanding of their affect on gene expression and  disease. We propose Hi-C-LSTM, a method that produces low-dimensional latent  representations that summarize intra-chromosomal Hi-C contacts via a recurrent  long short-term memory neural network model. We find that these representations  contain all the information needed to recreate the observed Hi-C matrix with high  accuracy, outperforming existing methods. These representations enable the  identification of a variety of conformation-defining genomic elements, including  nuclear compartments and conformation-related transcription factors. They  furthermore enable in-silico perturbation experiments that measure the influence  of cis-regulatory elements on conformation.", "journal": "Nature communications", "authors": ["Dsouza KB", "Maslova A", "Al-Jibury E", "Merkenschlager M", "Bhargava VK", "Libbrecht MW"], "@id": "/publications/716f318f-490c-468e-828f-e7dff0fb7110/", "date_published": "2022-06-28", "display_title": "Dsouza KB et al. (2022) PMID:35764630", "title": "Learning representations of chromatin contacts using a recurrent neural network  identifies genomic drivers of conformation.", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"status": "current", "uuid": "dfc530f1-82c0-4ddc-8f95-6f40417f87a0", "@type": ["Publication", "Item"], "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", "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"], "@id": "/publications/dfc530f1-82c0-4ddc-8f95-6f40417f87a0/", "date_published": "2021-09", "display_title": "Akgol Oksuz B et al. 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