Fiche publication
Date publication
octobre 2025
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARRETO Guillermo
Tous les auteurs :
Dou Y, Tetik-Elsherbiny N, Gao R, Ren Y, Chen YW, Merbecks M, Setya A, Lityagina O, Wang Y, Chichelnitskiy E, Abouissa A, Wu CC, Barreto G, Potente M, Wieland T, Ola R, Grieshaber P, Loukanov T, Gorenflo M, Heineke J, Cordero J, Dobreva G
Lien Pubmed
Résumé
Heart morphogenesis and function rely on intricate communication among distinct cardiac cell types. How their co-development and crosstalk are coordinated is largely unexplored. Our study unveils key functions of the histone H2B ubiquitin (H2Bub1) ligase RNF20 in second heart field development and cardiac endothelial cells. We demonstrate that RNF20 promotes Nrg1 expression through a RNF20-H2Bub1-dependent mechanism and restrains TGF-β signaling by influencing RNA polymerase II pause release at TGF-β target genes in endothelial cells. While heightened TGF-β signaling following RNF20 loss results endothelial-to-mesenchymal transition (EndMT), both impaired Nrg1 signaling and elevated TGF-β activity contribute to abnormal cardiomyocyte proliferation and contractility. Importantly, RNF20 expression is significantly reduced in cardiac endothelial cells from congenital heart disease patients showing a positive correlation with oxygen saturation and a negative correlation with key components and downstream effectors of TGF-β signaling. In summary, our work identifies a crucial role for RNF20 in safeguarding endothelial identity and physiological angiocrine signaling, thereby ensuring proper heart development and function.
Mots clés
Ubiquitin-Protein Ligases, metabolism, Humans, Signal Transduction, Animals, Heart Defects, Congenital, metabolism, Transforming Growth Factor beta, metabolism, Endothelial Cells, metabolism, Myocytes, Cardiac, metabolism, Mice, Epithelial-Mesenchymal Transition, Cell Proliferation, Heart, embryology, Male
Référence
Nat Commun. 2025 10 27;16(1):9480
