{"ID": "PMID:28355183", "lab": {"uuid": "82ebab19-8a20-47c5-baeb-9a08a9524b10", "status": "current", "title": "Leonid Mirny, MIT", "correspondence": [{"contact_email": "bGVvbmlkQG1pdC5lZHU=", "@id": "/users/f520d12a-e4c4-4774-a230-08d6dc4f5ef1/", "display_title": "Leonid Mirny"}], "@id": "/labs/leonid-mirny-lab/", "@type": ["Lab", "Item"], "display_title": "Leonid Mirny, MIT", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.82ebab19-8a20-47c5-baeb-9a08a9524b10"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/28355183", "award": {"uuid": "ae6c618f-7a8c-441e-a886-e30bbbe591da", "status": "current", "project": "4DN", "@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. 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", "name": "1U54DK107980-01", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Single-nucleus Hi-C reveals unique chromatin reorganization at oocyte-to-zygote transition.", "status": "current", "aliases": ["mirny-lab:snHiC_oocyte_ref"], "authors": ["Flyamer IM", "Gassler J", "Imakaev M", "Brandao HB", "Ulianov SV", "Abdennur N", "Razin SV", "Mirny LA", "Tachibana-Konwalski K"], "journal": "Nature", "abstract": "Chromatin is reprogrammed after fertilization to produce a totipotent zygote with the potential to generate a new organism. The maternal genome inherited from the  oocyte and the paternal genome provided by sperm coexist as separate haploid nuclei in the zygote. How these two epigenetically distinct genomes are spatially organized is poorly understood. Existing chromosome conformation capture-based methods are not applicable to oocytes and zygotes owing to a paucity of material. To study three-dimensional chromatin organization in rare cell types, we developed a single-nucleus Hi-C (high-resolution chromosome conformation capture) protocol that provides greater than tenfold more contacts per cell than the previous method. Here we show that chromatin architecture is uniquely reorganized during the oocyte-to-zygote transition in mice and is distinct in paternal and maternal nuclei within single-cell zygotes. Features of genomic organization including compartments, topologically associating domains (TADs) and loops are present in individual oocytes when averaged over the genome, but the presence of  each feature at a locus varies between cells. At the sub-megabase level, we observed stochastic clusters of contacts that can occur across TAD boundaries but average into TADs. Notably, we found that TADs and loops, but not compartments, are present in zygotic maternal chromatin, suggesting that these are generated by different mechanisms. Our results demonstrate that the global chromatin organization of zygote nuclei is fundamentally different from that of other interphase cells. An understanding of this zygotic chromatin 'ground state' could potentially provide insights into reprogramming cells to a state of totipotency.", "date_created": "2018-08-08T18:38:25.738913+00:00", "published_by": "4DN", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2018-08-30T18:44:32.198976+00:00"}, "date_published": "2017-03-29", "public_release": "2018-08-30", "schema_version": "2", "@id": "/publications/b742dd8d-fa19-4e6c-95ce-5fed1110bfa6/", "@type": ["Publication", "Item"], "uuid": "b742dd8d-fa19-4e6c-95ce-5fed1110bfa6", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Flyamer IM et al. (2017) PMID:28355183", "external_references": [], "short_attribution": "Flyamer IM et al. (2017)", "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}