{"ID": "PMID:40060486", "lab": {"@id": "/labs/bing-ren-lab/", "@type": ["Lab", "Item"], "status": "current", "title": "Bing Ren, UCSD", "display_title": "Bing Ren, UCSD", "uuid": "795847de-20b6-4f8c-ba8d-185215469cbf", "correspondence": [{"contact_email": "YmlyZW5AdWNzZC5lZHU=", "@id": "/users/e3159ffc-a5a9-43a1-8cfa-90b776c39788/", "display_title": "Bing Ren"}], "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.795847de-20b6-4f8c-ba8d-185215469cbf"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/40060486", "award": {"project": "4DN", "display_title": "CENTER FOR INTEGRATED MULTI-MODAL AND MULTI-SCALE NUCLEOME RESEARCH", "center_title": "CDIMV - Ren", "@type": ["Award", "Item"], "name": "1UM1HG011585-01", "@id": "/awards/1UM1HG011585-01/", "uuid": "ee89349a-1d43-4048-9142-bc750f0f3b32", "status": "current", "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.", "pi": {"error": "no view permissions"}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Context-Dependent and Gene-Specific Role of Chromatin Architecture Mediated by  Histone Modifiers and Loop-extrusion Machinery.", "status": "current", "aliases": ["4dn-dcic-lab:adam_jussila_loop_extrusion"], "authors": ["Tastemel M", "Jussila A", "Saravanan B", "Huang H", "Xie Y", "Zhu Q", "Jiang Y", "Armand E", "Ren B"], "journal": "bioRxiv : the preprint server for biology", "abstract": "Loop-extrusion machinery, comprising the cohesin complex and CCCTC-binding factor  CTCF, organizes the interphase chromosomes into topologically associating domains  (TADs) and loops, but acute depletion of components of this machinery results in  variable transcriptional changes in different cell types, highlighting the  complex relationship between chromatin organization and gene regulation. Here, we  systematically investigated the role of 3D genome architecture in gene regulation  in mouse embryonic stem cells under various perturbation conditions. We found  that acute depletion of cohesin or CTCF disrupts the formation of TADs, but  affects gene regulation in a gene-specific and context-dependent manner.  Furthermore, the loop extrusion machinery was dispensable for transcription from  most genes in steady state, consistent with prior results, but became critical  for a large number of genes during transition of cellular states. Through a  genome-wide CRISPR screen, we uncovered multiple factors that can modulate the  role of loop extrusion machinery in gene regulation in a gene-specific manner.  Among them were the MORF acetyltransferase complex members (Kat6b, Ing5, Brpf1),  which could antagonize the transcriptional insulation mediated by CTCF and  cohesin complex at developmental genes. Interestingly, inhibition of Kat6b  partially rescues the insulator defects in cells lacking the cohesin loader  Nipbl, mutations of which are responsible for the developmental disorder Cornelia  de Lange syndrome. Taken together, our findings uncovered interplays between the  loop extrusion machinery and histone modifying complex that underscore the  context-dependent and gene-specific role of the 3D genome.", "date_created": "2025-06-25T17:32:13.557768+00:00", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2025-06-25T17:47:00.509184+00:00"}, "date_published": "2025-02-26", "public_release": "2025-06-25", "schema_version": "2", "project_release": "2025-06-25", "exp_sets_prod_in_pub": [{"display_title": "4DNESI7RG1SM", "@id": "/experiment-set-replicates/4DNESI7RG1SM/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNESI7RG1SM", "uuid": "63679646-6798-4118-b653-628b53d41714", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEX7B4TNTB/", "uuid": "20235761-af1b-43e3-afaf-f562a6331dd6", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEX7B4TNTB", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNES3QUSY1F", "@id": "/experiment-set-replicates/4DNES3QUSY1F/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNES3QUSY1F", "uuid": "d9d51e46-9019-4d7c-9b26-72da3ba48cce", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEX8Z284OF/", "uuid": "07f6b8f3-20b1-4e23-ae7e-a7c0e116b94f", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEX8Z284OF", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNES9946GB9", "@id": "/experiment-set-replicates/4DNES9946GB9/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNES9946GB9", "uuid": "e8606dc0-3e88-4f2a-8d2c-6d1c5b6b168d", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEXR61ZVQ1/", "uuid": "a2498bf6-6eed-44bd-ae87-bffd9763491e", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEXR61ZVQ1", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNESKBC3QBS", "@id": "/experiment-set-replicates/4DNESKBC3QBS/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNESKBC3QBS", "uuid": "7d2a9c5c-8209-41cc-b1b8-eae2016c59ca", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEXU2GDGY4/", "uuid": "37ea6875-79fe-4149-9449-b2b45b737b1a", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEXU2GDGY4", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNESX8IACI3", "@id": "/experiment-set-replicates/4DNESX8IACI3/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNESX8IACI3", "uuid": "1397eac2-e83c-4ab4-a8e7-52760d9bce79", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEX9XO67T2/", "uuid": "f045b35d-642f-47a8-a7be-3614deac9c26", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEX9XO67T2", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNESG53SEUU", "@id": "/experiment-set-replicates/4DNESG53SEUU/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNESG53SEUU", "uuid": "8820f58a-aab3-4df9-8c0c-92c707ecbb13", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEX9XXD7C8/", "uuid": "51e41093-1c14-4971-a4c2-2d006a2cc171", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEX9XXD7C8", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNES2LZ7D8W", "@id": "/experiment-set-replicates/4DNES2LZ7D8W/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNES2LZ7D8W", "uuid": "fe0d071e-d5b1-4b8f-979a-d57833a1dde9", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEXAGALPNQ/", "uuid": "a1e8b86c-2abf-439a-9726-e491f4522e65", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEXAGALPNQ", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNESE2MH977", "@id": "/experiment-set-replicates/4DNESE2MH977/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNESE2MH977", "uuid": "89b1c1ea-a429-4ad1-a13b-8f97d6d388c5", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEXYPSCL48/", "uuid": "cbdafb6f-2a86-4e77-b9bc-4b352bb66e3b", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEXYPSCL48", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNESTLJOO1C", "@id": "/experiment-set-replicates/4DNESTLJOO1C/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNESTLJOO1C", "uuid": "bb8ef03a-6f11-46bc-9fb3-6c762eaa9aff", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEXYQ1XZLY/", "uuid": "6880338d-de39-4972-ac87-4f96f9fdc151", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEXYQ1XZLY", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNESQD7KQVS", "@id": "/experiment-set-replicates/4DNESQD7KQVS/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNESQD7KQVS", "uuid": "74f1c9ba-668e-4994-a98b-899c2b7c8c36", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEXYNSCQZP/", "uuid": "4b14a35d-0da4-4c2f-9537-b2ee7ae935c0", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEXYNSCQZP", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"display_title": "4DNESJ15KEBD", "@id": "/experiment-set-replicates/4DNESJ15KEBD/", "experimentset_type": "replicate", "status": "released", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "accession": "4DNESJ15KEBD", "uuid": "0fbcb4f0-9d93-4a0c-887f-e45a3b3106af", "experiments_in_set": [{"status": "released", "@id": "/experiments-mic/4DNEXI516O1G/", "uuid": "73d5cf78-bbae-4572-9159-c364f8abe154", "@type": ["ExperimentMic", "Experiment", "Item"], "display_title": "multiplexed FISH on F123-CASTx129 with Sox2 tags and RMCE site between Sox2 and its SE - 4DNEXI516O1G", "experiment_type": {"@id": "/experiment-types/multiplexed-fish/", "uuid": "bcdda46a-489d-4d22-be80-c9c21552c915", "display_title": "multiplexed FISH", "status": "released", "@type": ["ExperimentType", "Item"], "title": "multiplexed FISH", "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/7b338c4e-a510-41ff-b65a-389b1e270c97/", "@type": ["Publication", "Item"], "uuid": "7b338c4e-a510-41ff-b65a-389b1e270c97", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Tastemel M et al. (2025) PMID:40060486", "external_references": [], "short_attribution": "Tastemel M et al. (2025)", "number_of_experiment_sets": 11, "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}