{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Riching AS"],"funding":["American Heart Association","NCATS NIH HHS","NIDDK NIH HHS","NIA NIH HHS","National Heart, Lung, and Blood Institute","NHLBI NIH HHS","NCI NIH HHS","Colorado Clinical and Translational Sciences Institute","CIHR"],"pagination":["44-59"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8809092"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["153"],"pubmed_abstract":["Direct reprogramming of fibroblasts into cardiomyocytes (CMs) represents a promising strategy to regenerate CMs lost after ischemic heart injury. Overexpression of GATA4, HAND2, MEF2C, TBX5, miR-1, and miR-133 (GHMT2m) along with transforming growth factor beta (TGF-β) inhibition efficiently promote 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) that is associated with congenital heart disease exhibits reduced binding to JMJD3 and impairs cardiomyogenesis. Thus, we have identified an epigenetic mechanism wherein canonical TGF-β pathway activation impairs cardiac gene programming, in part by interfering with GATA4-JMJD3 interactions."],"journal":["Journal of molecular and cellular cardiology"],"pubmed_title":["Suppression of canonical TGF-β signaling enables GATA4 to interact with H3K27me3 demethylase JMJD3 to promote cardiomyogenesis."],"pmcid":["PMC8809092"],"funding_grant_id":["FRN-216927","R01 AG067664","R01 HL127240","R01 HL147558","R01 CA252707","R01 HL150225","R01 HL133230","R01 DK119594","R01 HL116848","TL1 TR001081"],"pubmed_authors":["Bagchi RA","Song K","Riching AS","Klein BJ","Buttrick PM","Cao Y","Chi C","McKinsey TA","Xu H","Danis E","Zhao Y","Kutateladze TG"],"additional_accession":[]},"is_claimable":false,"name":"Suppression of canonical TGF-β signaling enables GATA4 to interact with H3K27me3 demethylase JMJD3 to promote cardiomyogenesis.","description":"Direct reprogramming of fibroblasts into cardiomyocytes (CMs) represents a promising strategy to regenerate CMs lost after ischemic heart injury. Overexpression of GATA4, HAND2, MEF2C, TBX5, miR-1, and miR-133 (GHMT2m) along with transforming growth factor beta (TGF-β) inhibition efficiently promote 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) that is associated with congenital heart disease exhibits reduced binding to JMJD3 and impairs cardiomyogenesis. Thus, we have identified an epigenetic mechanism wherein canonical TGF-β pathway activation impairs cardiac gene programming, in part by interfering with GATA4-JMJD3 interactions.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2025-04-04T22:04:18.789Z","creation":"2025-04-04T22:04:18.789Z"},"accession":"S-EPMC8809092","cross_references":{"pubmed":["33359755"],"doi":["10.1016/j.yjmcc.2020.12.005"]}}