{"doi":"10.1101/2020.02.12.945790","title":"Suppression of canonical TGF-β signaling enables GATA4 to interact with H3K27me3 demethylase JMJD3 to promote cardiomyogenesis","abstract":"Summary Direct reprogramming of fibroblasts into cardiomyocytes (CMs) represents a promising strategy to regenerate CMs lost after ischemic heart injury. Overexpression of G ATA4, H AND2, M EF2C, T BX5, miR-1, and miR-133 (GHMT2m) along with transforming growth factor beta (TGF-β) inhibition efficiently promotes reprogramming. However, the mechanisms by which TGF-β blockade promotes cardiac reprogramming remain unknown. Here, we identify interactions between the histone H3 lysine 27 trimethylation (H3K27me3) – demethylase JMJD3, the SWI/SNF remodeling complex subunit BRG1, and cardiac transcription factors. Furthermore, canonical TGF-β signaling regulates the interaction between GATA4 and JMJD3. TGF-β activation impairs the ability of GATA4 to bind target genes and prevents demethylation of H3K27 at cardiac gene promoters during cardiac reprogramming. Finally, a mutation in GATA4 (V267M) exhibits reduced binding to JMJD3 and impaired cardiomyogenesis. Thus, we have identified an epigenetic mechanism wherein canonical TGF-β pathway activation impairs cardiac gene programming by interfering with GATA4-JMJD3 interactions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":124614,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"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":310928,"name":"Etienne Danis","orcid":"0000-0002-5651-8111","position":1,"is_corresponding":false},{"id":570416,"name":"Yuanbiao Zhao","orcid":null,"position":2,"is_corresponding":false},{"id":570417,"name":"Yingqiong Cao","orcid":null,"position":3,"is_corresponding":false},{"id":404925,"name":"Congwu Chi","orcid":"0000-0002-2225-6221","position":4,"is_corresponding":false},{"id":569732,"name":"Rushita A. Bagchi","orcid":"0000-0002-9075-0766","position":5,"is_corresponding":false},{"id":479326,"name":"Brianna J. Klein","orcid":"0000-0003-2479-8013","position":6,"is_corresponding":false},{"id":569733,"name":"Hongyan Xu","orcid":"0000-0001-7432-9018","position":7,"is_corresponding":false},{"id":314067,"name":"Tatiana G. Kutateladze","orcid":"0000-0001-7375-6990","position":8,"is_corresponding":false},{"id":45204,"name":"Timothy A. McKinsey","orcid":"0000-0001-7778-4470","position":9,"is_corresponding":false},{"id":350886,"name":"Peter M. Buttrick","orcid":"0000-0002-5692-2691","position":10,"is_corresponding":false},{"id":403878,"name":"Kunhua Song","orcid":"0000-0003-3805-4509","position":11,"is_corresponding":false},{"id":473081,"name":"Andrew S. Riching","orcid":"0000-0001-6797-6487","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T23:15:11.632153Z","pmid":null,"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":[]}