{"doi":"10.1161/circulationaha.120.047753","title":"BRD4 (Bromodomain-Containing Protein 4) Interacts with GATA4 (GATA Binding Protein 4) to Govern Mitochondrial Homeostasis in Adult Cardiomyocytes","abstract":"Background: Gene regulatory networks control tissue homeostasis and disease progression in a cell type–specific manner. Ubiquitously expressed chromatin regulators modulate these networks, yet the mechanisms governing how tissue specificity of their function is achieved are poorly understood. BRD4 (bromodomain-containing protein 4), a member of the BET (bromo- and extraterminal domain) family of ubiquitously expressed acetyl-lysine reader proteins, plays a pivotal role as a coactivator of enhancer signaling across diverse tissue types in both health and disease and has been implicated as a pharmacological target in heart failure. However, the cell-specific role of BRD4 in adult cardiomyocytes remains unknown. Methods: We combined conditional mouse genetics, unbiased transcriptomic and epigenomic analyses, and classic molecular biology and biochemical approaches to understand the mechanism by which BRD4 in adult cardiomyocyte homeostasis. Results: Here, we show that cardiomyocyte-specific deletion of Brd4 in adult mice leads to acute deterioration of cardiac contractile function with mutant animals demonstrating a transcriptomic signature characterized by decreased expression of genes critical for mitochondrial energy production. Genome-wide occupancy data show that BRD4 enriches at many downregulated genes (including the master coactivators Ppargc1a, Ppargc1b , and their downstream targets) and preferentially colocalizes with GATA4 (GATA binding protein 4), a lineage-determining cardiac transcription factor not previously implicated in regulation of adult cardiac metabolism. BRD4 and GATA4 form an endogenous complex in cardiomyocytes and interact in a bromodomain-independent manner, revealing a new functional interaction partner for BRD4 that can direct its locus and tissue specificity. Conclusions: These results highlight a novel role for a BRD4-GATA4 module in cooperative regulation of a cardiomyocyte-specific gene program governing bioenergetic homeostasis in the adult heart.","journal":"Circulation","year":2020,"id":61974,"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":54,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":56513,"name":"Michael Alexanian","orcid":"0000-0001-6224-6354","position":1,"is_corresponding":false},{"id":328004,"name":"Ricardo Linares-Saldana","orcid":"0000-0003-2657-825X","position":2,"is_corresponding":false},{"id":328005,"name":"Bárbara González‐Terán","orcid":"0000-0002-4336-8644","position":3,"is_corresponding":false},{"id":56514,"name":"Gaia Andreoletti","orcid":"0000-0002-0452-0009","position":4,"is_corresponding":false},{"id":278557,"name":"Yu Huang","orcid":"0000-0002-9331-728X","position":5,"is_corresponding":false},{"id":270193,"name":"Andrew J. Connolly","orcid":"0000-0002-0660-3270","position":6,"is_corresponding":false},{"id":328006,"name":"Wonho Kim","orcid":"0000-0002-5070-8328","position":7,"is_corresponding":false},{"id":3385,"name":"Austin Hsu","orcid":"0000-0002-4361-4358","position":8,"is_corresponding":false},{"id":328007,"name":"Qiming Duan","orcid":"0000-0002-6204-3028","position":9,"is_corresponding":false},{"id":328008,"name":"Sarah A. B. Winchester","orcid":"0000-0003-2924-4757","position":10,"is_corresponding":false},{"id":328009,"name":"Franco Felix","orcid":"0000-0002-4297-7149","position":11,"is_corresponding":false},{"id":328010,"name":"Juan A. Pérez-Bermejo","orcid":"0000-0001-7625-358X","position":12,"is_corresponding":false},{"id":328011,"name":"Qiaohong Wang","orcid":"0000-0001-9225-1963","position":13,"is_corresponding":false},{"id":328012,"name":"Li Li","orcid":"0000-0003-2342-3658","position":14,"is_corresponding":false},{"id":328013,"name":"Parisha P. Shah","orcid":"0000-0002-7756-6868","position":15,"is_corresponding":false},{"id":236209,"name":"Saptarsi M. Haldar","orcid":"0000-0001-7968-9696","position":16,"is_corresponding":false},{"id":328014,"name":"Rajan Jain","orcid":"0000-0002-1979-044X","position":17,"is_corresponding":false},{"id":251046,"name":"Deepak Srivastava","orcid":"0000-0002-3480-5953","position":18,"is_corresponding":false},{"id":328003,"name":"Arun Padmanabhan","orcid":"0000-0002-6806-3046","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T21:10:11.612909Z","pmid":"33094644","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":[]}