{"ID": "PMID:35637420", "lab": {"display_title": "External Lab", "@type": ["Lab", "Item"], "uuid": "d3412190-317a-4837-823f-3892b9f641a4", "title": "External Lab", "status": "current", "@id": "/labs/external-lab/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin", "role.lab_submitter", "submits_for.d3412190-317a-4837-823f-3892b9f641a4"]}}, "url": "https://www.ncbi.nlm.nih.gov/pubmed/35637420", "tags": ["4dn-external-reuse"], "award": {"uuid": "12a92962-8265-4fc0-b2f8-cf14f05db58b", "@type": ["Award", "Item"], "description": "Funding source is from outside 4DN.", "center_title": "External", "project": "External", "center": "External", "name": "external-award", "display_title": "EXTERNAL AWARD", "status": "current", "@id": "/awards/external-award/", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, "title": "Identifying synergistic high-order 3D chromatin conformations from genome-scale  nanopore concatemer sequencing.", "status": "current", "aliases": ["4dn-dcic-lab:PMID:35637420"], "authors": ["Deshpande AS", "Ulahannan N", "Pendleton M", "Dai X", "Ly L", "Behr JM", "Schwenk S", "Liao W", "Augello MA", "Tyer C", "Rughani P", "Kudman S", "Tian H", "Otis HG", "Adney E", "Wilkes D", "Mosquera JM", "Barbieri CE", "Melnick A", "Stoddart D", "Turner DJ", "Juul S", "Harrington E", "Imielinski M"], "journal": "Nature biotechnology", "abstract": "High-order three-dimensional (3D) interactions between more than two genomic loci  are common in human chromatin, but their role in gene regulation is unclear.  Previous high-order 3D chromatin assays either measure distant interactions  across the genome or proximal interactions at selected targets. To address this  gap, we developed Pore-C, which combines chromatin conformation capture with  nanopore sequencing of concatemers to profile proximal high-order chromatin  contacts at the genome scale. We also developed the statistical method Chromunity  to identify sets of genomic loci with frequencies of high-order contacts  significantly higher than background ('synergies'). Applying these methods to  human cell lines, we found that synergies were enriched in enhancers and  promoters in active chromatin and in highly transcribed and lineage-defining  genes. In prostate cancer cells, these included binding sites of androgen-driven  transcription factors and the promoters of androgen-regulated genes. Concatemers  of high-order contacts in highly expressed genes were demethylated relative to  pairwise contacts at the same loci. Synergies in breast cancer cells were  associated with tyfonas, a class of complex DNA amplicons. These results  rigorously link genome-wide high-order 3D interactions to lineage-defining  transcriptional programs and establish Pore-C and Chromunity as scalable  approaches to assess high-order genome structure.", "categories": ["integrative analysis"], "date_created": "2024-02-14T19:51:05.431151+00:00", "published_by": "External", "submitted_by": {"error": "no view permissions"}, "last_modified": {"modified_by": {"error": "no view permissions"}, "date_modified": "2024-03-15T15:45:24.899427+00:00"}, "date_published": "2022-10", "public_release": "2024-03-15", "schema_version": "2", "project_release": "2024-03-15", "exp_sets_used_in_pub": [{"uuid": "cddd45d8-fbec-4806-a63b-6c16c5bd3138", "display_title": "4DNESI1U7ZW9", "experimentset_type": "replicate", "@id": "/experiment-set-replicates/4DNESI1U7ZW9/", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"uuid": "aa6f0d82-16c9-4109-a1f8-3fa0636a3560", "display_title": "4DNES3JX38V5", "experimentset_type": "replicate", "@id": "/experiment-set-replicates/4DNES3JX38V5/", "@type": ["ExperimentSetReplicate", "ExperimentSet", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}, {"uuid": "b5e7dbe9-6ebe-468e-8d02-45ff6ca04ce8", "display_title": "4DNESEOQUGG3", "experimentset_type": "custom", "@id": "/experiment-sets/4DNESEOQUGG3/", "@type": ["ExperimentSet", "Item"], "status": "released", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}}], "@id": "/publications/b78174a0-b747-4826-bdd6-276e6697c5f2/", "@type": ["Publication", "Item"], "uuid": "b78174a0-b747-4826-bdd6-276e6697c5f2", "principals_allowed": {"view": ["system.Everyone"], "edit": ["group.admin"]}, "display_title": "Deshpande AS et al. (2022) PMID:35637420", "external_references": [], "short_attribution": "Deshpande AS et al. (2022)", "@context": "/terms/", "aggregated-items": {}, "validation-errors": []}