CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis

Détails

Ressource 1Télécharger: BIB_313C4A6D486A.P001.pdf (2900.85 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_313C4A6D486A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis
Périodique
Journal of Molecular and Cellular Cardiology
Auteur(s)
Ounzain S., Micheletti R., Arnan C., Plaisance I., Cecchi D., Schroen B., Reverter F., Alexanian M., Gonzales C., Ng S.Y., Bussotti G., Pezzuto I., Notredame C., Heymans S., Guigó R. , Johnson R., Pedrazzini T.
ISSN
1095-8584 (Electronic)
ISSN-L
0022-2828
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
89
Numéro
Pt A
Pages
98-9112
Langue
anglais
Notes
Publication types: Journal Article Publication Status: ppublish
Résumé
Long noncoding RNAs (lncRNAs) are emerging as important regulators of developmental pathways. However, their roles in human cardiac precursor cell (CPC) remain unexplored. To characterize the long noncoding transcriptome during human CPC cardiac differentiation, we profiled the lncRNA transcriptome in CPCs isolated from the human fetal heart and identified 570 lncRNAs that were modulated during cardiac differentiation. Many of these were associated with active cardiac enhancer and super enhancers (SE) with their expression being correlated with proximal cardiac genes. One of the most upregulated lncRNAs was a SE-associated lncRNA that was named CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA. CARMEN exhibits RNA-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. Interestingly, CARMEN interacts with SUZ12 and EZH2, two components of the polycomb repressive complex 2 (PRC2). We demonstrate that CARMEN knockdown inhibits cardiac specification and differentiation in cardiac precursor cells independently of MIR-143 and -145 expression, two microRNAs located proximal to the enhancer sequences. Importantly, CARMEN expression was activated during pathological remodeling in the mouse and human hearts, and was necessary for maintaining cardiac identity in differentiated cardiomyocytes. This study demonstrates therefore that CARMEN is a crucial regulator of cardiac cell differentiation and homeostasis.
Mots-clé
Body Patterning/genetics, Cell Differentiation/genetics, Cell Lineage/genetics, Enhancer Elements, Genetic/genetics, Heart/embryology, Homeostasis/genetics, Myocardium/pathology, Polycomb Repressive Complex 2/metabolism, RNA, Long Noncoding/genetics, RNA, Long Noncoding/metabolism, Stem Cells/cytology, Transcriptome/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/10/2016 15:29
Dernière modification de la notice
20/08/2019 13:16
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