serval:BIB_313C4A6D486A
CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis
10.1016/j.yjmcc.2015.09.016
000367212800013
26423156
Ounzain
S.
author
Micheletti
R.
author
Arnan
C.
author
Plaisance
I.
author
Cecchi
D.
author
Schroen
B.
author
Reverter
F.
author
Alexanian
M.
author
Gonzales
C.
author
Ng
S.Y.
author
Bussotti
G.
author
Pezzuto
I.
author
Notredame
C.
author
Heymans
S.
author
Guigó R.
author
Johnson
R.
author
Pedrazzini
T.
author
article
2015
Journal of Molecular and Cellular Cardiology
1095-8584
0022-2828
journal
89
Pt A
98-9112
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.
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
eng
60_published
true
peer-reviewed
Publication types: Journal Article Publication Status: ppublish
University of Lausanne
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