{"doi":"10.1172/jci153635","title":"Global chromatin landscapes identify candidate noncoding modifiers of cardiac rhythm","abstract":"Comprehensive cis-regulatory landscapes are essential for accurate enhancer prediction and disease variant mapping. Although cis-regulatory element (CRE) resources exist for most tissues and organs, many rare - yet functionally important - cell types remain overlooked. Despite representing only a small fraction of the heart's cellular biomass, the cardiac conduction system (CCS) unfailingly coordinates every life-sustaining heartbeat. To globally profile the mouse CCS cis-regulatory landscape, we genetically tagged CCS component-specific nuclei for comprehensive assay for transposase-accessible chromatin-sequencing (ATAC-Seq) analysis. Thus, we established a global CCS-enriched CRE database, referred to as CCS-ATAC, as a key resource for studying CCS-wide and component-specific regulatory functions. Using transcription factor (TF) motifs to construct CCS component-specific gene regulatory networks (GRNs), we identified and independently confirmed several specific TF sub-networks. Highlighting the functional importance of CCS-ATAC, we also validated numerous CCS-enriched enhancer elements and suggested gene targets based on CCS single-cell RNA-Seq data. Furthermore, we leveraged CCS-ATAC to improve annotation of existing human variants related to cardiac rhythm and nominated a potential enhancer-target pair that was dysregulated by a specific SNP. Collectively, our results established a CCS-regulatory compendium, identified novel CCS enhancer elements, and illuminated potential functional associations between human genomic variants and CCS component-specific CREs.","journal":"Journal of Clinical Investigation","year":2022,"id":277296,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9381,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":354953,"name":"Rahul K. Kollipara","orcid":null,"position":1,"is_corresponding":false},{"id":948855,"name":"Gabriela Orquera-Tornakian","orcid":null,"position":2,"is_corresponding":false},{"id":948376,"name":"Sean C. Goetsch","orcid":"0000-0003-1141-683X","position":3,"is_corresponding":false},{"id":352533,"name":"Minzhe Zhang","orcid":"0000-0002-4555-1928","position":4,"is_corresponding":false},{"id":948377,"name":"Cameron Perry","orcid":"0000-0001-5254-581X","position":5,"is_corresponding":false},{"id":797249,"name":"Boxun Li","orcid":"0000-0002-4516-4418","position":6,"is_corresponding":false},{"id":255299,"name":"John M. Shelton","orcid":"0000-0002-2949-1638","position":7,"is_corresponding":false},{"id":741522,"name":"Minoti Bhakta","orcid":null,"position":8,"is_corresponding":false},{"id":726897,"name":"Jialei Duan","orcid":"0000-0003-4086-7461","position":9,"is_corresponding":false},{"id":326811,"name":"Yang Xie","orcid":"0000-0001-9456-1762","position":10,"is_corresponding":false},{"id":27515,"name":"Guanghua Xiao","orcid":"0000-0001-9387-9883","position":11,"is_corresponding":false},{"id":285068,"name":"Bret M. Evers","orcid":"0000-0001-5686-0315","position":12,"is_corresponding":false},{"id":284865,"name":"Gary C. Hon","orcid":"0000-0002-1615-0391","position":13,"is_corresponding":false},{"id":385824,"name":"Ralf Kittler","orcid":"0000-0002-0098-6792","position":14,"is_corresponding":false},{"id":43087,"name":"Nikhil Munshi","orcid":"0000-0002-8397-100X","position":15,"is_corresponding":false},{"id":550839,"name":"Samadrita Bhattacharyya","orcid":"0000-0002-2709-3804","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T00:28:34.768552Z","pmid":"36454649","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}