{"ID": "PMID:38766012", "lab": {"status": "current", "@type": ["Lab", "Item"], "@id": "/labs/ana-pombo-lab/", "correspondence": [{"contact_email": "YW5hLnBvbWJvQG1kYy1iZXJsaW4uZGU=", "@id": "/users/bce4f2b5-9a2a-4db2-9dd6-7d61f19025c1/", "display_title": "Ana Pombo"}], "uuid": "cf5abe29-1cf9-4413-b02e-664b47a6d53d", "display_title": "Ana Pombo, MDC", "title": "Ana Pombo, MDC", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.cf5abe29-1cf9-4413-b02e-664b47a6d53d"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/38766012", "award": {"@id": "/awards/1UM1HG011585-01/", "name": "1UM1HG011585-01", "description": "CDIMV: The transcriptional regulatory sequences communicate with each other dynamically in the 3D nuclear space to direct cell type specific gene expression. Currently, a major barrier to understanding the transcriptional regulatory programs is the lack of tools, models and maps to explore the chromatin architecture in diverse cell types and physiological contexts. We will address this pressing need by deploying transformative technologies to study the chromatin architecture in mammalian cells at an unprecedented resolution and scale. Specifically, we will generate navigable, cell-type-specific reference maps of chromatin architecture in the mouse, macaque and human brains by integrating high resolution and high throughput imaging and orthogonal single-cell-based genomic methods. We will also dissect the role of chromatin architecture in gene regulation through a set of controlled perturbation experiments in the mouse ES cells (ESC) and ESC-derived neural progenitor cells (NPC). We will develop structural models of chromatin organization with advanced polymer physics and statistical learning methods, and validate their predictive power in embryonic stem cells and in ex vivo brain slices. Finally, we will make the reference maps, analytical tools, visualization methods and structural models available to the broader community. The proposed research project will dramatically transform our ability to analyze the 4D Nucleome of complex tissues, and produce the much-needed maps, tools and models for understanding the gene regulatory programs encoded in the linear genome sequences.", "display_title": "CENTER FOR INTEGRATED MULTI-MODAL AND MULTI-SCALE NUCLEOME RESEARCH", "center_title": "CDIMV - Ren", "uuid": "ee89349a-1d43-4048-9142-bc750f0f3b32", "project": "4DN", "@type": ["Award", "Item"], "status": "current", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Extensive folding variability between homologous chromosomes in mammalian cells.", "status": "current", "aliases": ["4dn-dcic-lab:PMID_38766012_F123_GAM"], "authors": ["Irastorza-Azcarate I", "Kukalev A", "Kempfer R", "Thieme CJ", "Mastrobuoni G", "Markowski J", "Loof G", "Sparks TM", "Brookes E", "Natarajan KN", "Sauer S", "Fisher AG", "Nicodemi M", "Ren B", "Schwarz RF", "Kempa S", "Pombo A"], "journal": "bioRxiv : the preprint server for biology", "abstract": "Genetic variation and 3D chromatin structure have major roles in gene regulation.  Due to challenges in mapping chromatin conformation with haplotype-specific  resolution, the effects of genetic sequence variation on 3D genome structure and  gene expression imbalance remain understudied. Here, we applied Genome  Architecture Mapping (GAM) to a hybrid mouse embryonic stem cell (mESC) line with  high density of single nucleotide polymorphisms (SNPs). GAM resolved  haplotype-specific 3D genome structures with high sensitivity, revealing  extensive allelic differences in chromatin compartments, topologically  associating domains (TADs), long-range enhancer-promoter contacts, and CTCF  loops. Architectural differences often coincide with allele-specific differences  in gene expression, mediated by Polycomb repression. We show that histone genes  are expressed with allelic imbalance in mESCs, are involved in haplotype-specific  chromatin contact marked by H3K27me3, and are targets of Polycomb repression  through conditional knockouts of Ezh2 or Ring1b. Our work reveals highly distinct  3D folding structures between homologous chromosomes, and highlights their  intricate connections with allelic gene expression.", "categories": ["basic biology"], "date_created": "2024-05-22T17:12:35.739566+00:00", "published_by": "4DN", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-05-22T17:15:07.734059+00:00"}, "date_published": "2024-05-10", "public_release": "2024-05-22", "schema_version": "2", "project_release": "2024-05-22", "exp_sets_prod_in_pub": [{"status": "released", "display_title": "4DNESRQDNG61", "@id": "/experiment-set-replicates/4DNESRQDNG61/", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "uuid": "01b4333b-8008-4aac-b966-591b8aa98c9a", "experimentset_type": "replicate", "accession": "4DNESRQDNG61", "experiments_in_set": [{"uuid": "b0fee370-48b1-443d-9163-f97b6af29cd5", "@type": ["ExperimentSeq", "Experiment", "Item"], "@id": "/experiments-seq/4DNEX1KG9YVX/", "display_title": "GAM on F123-CASTx129 (Tier 2) - 4DNEX1KG9YVX", "status": "released", "experiment_type": {"@id": "/experiment-types/gam/", "title": "GAM", "status": "released", "@type": ["ExperimentType", "Item"], "display_title": "GAM", "uuid": "1c41d7cc-8bfb-402f-b752-9db223de86f4", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"uuid": "2b074ff4-713f-40b3-b2c2-c08a477382b2", "@type": ["ExperimentSeq", "Experiment", "Item"], "@id": "/experiments-seq/4DNEXOWEU1HW/", "display_title": "GAM on F123-CASTx129 (Tier 2) - 4DNEXOWEU1HW", "status": "released", "experiment_type": {"@id": "/experiment-types/gam/", "title": "GAM", "status": "released", "@type": ["ExperimentType", "Item"], "display_title": "GAM", "uuid": "1c41d7cc-8bfb-402f-b752-9db223de86f4", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@id": "/publications/cf26b7d2-d57e-467f-8509-d873abdad0bc/", "@type": ["Publication", "Item"], "uuid": "cf26b7d2-d57e-467f-8509-d873abdad0bc", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Irastorza-Azcarate I et al. (2024) PMID:38766012", "external_references": [], "short_attribution": "Irastorza-Azcarate I et al. (2024)", "number_of_experiment_sets": 1, "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}