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CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis
- Source :
- Journal of Molecular and Cellular Cardiology, vol. 89, no. Pt A, pp. 98-9112, Journal of Molecular and Cellular Cardiology, 89, 98-112. ELSEVIER SCI LTD
- Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Cellular differentiation
Cardiac precursor cells
Heart failure
Biology
Transcriptome
Mice
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
Super-enhancer
Cardiac development
microRNA
Regulació genètica
Animals
Homeostasis
Humans
Cell Lineage
Enhancer of Zeste Homolog 2 Protein
Enhancer
Molecular Biology
Body Patterning
Genetics
Regulation of gene expression
Gene Expression Profiling
Myocardium
Stem Cells
Polycomb Repressive Complex 2
Gene Expression Regulation, Developmental
Cell Differentiation
Heart
Super enhancer
Long non-coding RNA
Cell biology
Gene regulation
Enhancer Elements, Genetic
Gene Knockdown Techniques
biology.protein
RNA
RNA, Long Noncoding
Cardiology and Cardiovascular Medicine
PRC2
Long noncoding RNA
Subjects
Details
- Language :
- English
- ISSN :
- 00222828
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular and Cellular Cardiology
- Accession number :
- edsair.doi.dedup.....4a08b6260d9b2ac398bfc100644dc136