{"ID": "PMID:38766140", "lab": {"correspondence": [{"contact_email": "YW5hLnBvbWJvQG1kYy1iZXJsaW4uZGU=", "@id": "/users/bce4f2b5-9a2a-4db2-9dd6-7d61f19025c1/", "display_title": "Ana Pombo"}], "uuid": "cf5abe29-1cf9-4413-b02e-664b47a6d53d", "title": "Ana Pombo, MDC", "status": "current", "display_title": "Ana Pombo, MDC", "@id": "/labs/ana-pombo-lab/", "@type": ["Lab", "Item"], "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/38766140", "award": {"name": "1UM1HG011585-01", "@id": "/awards/1UM1HG011585-01/", "status": "current", "project": "4DN", "center_title": "CDIMV - Ren", "uuid": "ee89349a-1d43-4048-9142-bc750f0f3b32", "@type": ["Award", "Item"], "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", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "A single dose of cocaine rewires the 3D genome structure of midbrain dopamine  neurons.", "status": "current", "aliases": ["4dn-dcic-lab:PMID_38766140_GAM_cocaine"], "authors": ["Szabo D", "Franke V", "Bianco S", "Batiuk MY", "Paul EJ", "Kukalev A", "Pfisterer UG", "Irastorza-Azcarate I", "Chiariello AM", "Demharter S", "Zea-Redondo L", "Lopez-Atalaya JP", "Nicodemi M", "Akalin A", "Khodosevich K", "Ungless MA", "Winick-Ng W", "Pombo A"], "journal": "bioRxiv : the preprint server for biology", "abstract": "Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs  and play key roles in chronic drug usage (1-3) . As the synaptic and  transcriptional changes that follow an acute cocaine exposure are mostly resolved  within a few days (4,5) , the molecular changes that encode the long-term  cellular memory of the exposure within DNs remain unknown. To investigate whether  a single cocaine exposure induces long-term changes in the 3D genome structure of  DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic  analyses in the mouse midbrain. We found extensive rewiring of 3D genome  architecture at 24 hours past exposure which remains or worsens by 14 days,  outlasting transcriptional responses. The cocaine-induced chromatin rewiring  occurs at all genomic scales and affects genes with major roles in  cocaine-induced synaptic changes. A single cocaine exposure triggers extensive  long-lasting changes in chromatin condensation in post-synaptic and  post-transcriptional regulatory genes, for example the unfolding of Rbfox1 which  becomes most prominent 14 days post exposure. Finally, structurally remodeled  genes are most expressed in a specific DN sub-type characterized by low  expression of the dopamine auto-receptor Drd2 , a key feature of highly  cocaine-sensitive cells. These results reveal an important role for long-lasting  3D genome remodelling in the cellular memory of a single cocaine exposure,  providing new hypotheses for understanding the inception of drug addiction and 3D  genome plasticity.", "categories": ["model organism biology"], "date_created": "2024-05-22T17:25:42.843299+00:00", "published_by": "4DN", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-05-23T13:20:59.819023+00:00"}, "date_published": "2024-05-12", "public_release": "2024-05-22", "schema_version": "2", "project_release": "2024-05-22", "exp_sets_prod_in_pub": [{"display_title": "4DNESVF6WL86", "uuid": "d5984ca2-40b2-4db6-b708-79b04bf4de88", "accession": "4DNESVF6WL86", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "@id": "/experiment-set-replicates/4DNESVF6WL86/", "status": "released", "experimentset_type": "replicate", "experiments_in_set": [{"@id": "/experiments-seq/4DNEXW57SFU1/", "status": "released", "uuid": "5cec579b-7daa-4eb1-8e96-a58ee62ca4e3", "display_title": "GAM on ventral tegmental area - 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