CARMEN

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Entry NameAlias
CARMEN Cardiac Mesoderm Enchancer-Associated Noncoding RNA, ENSG00000249669, AK087736 (mouse Ortholog )
Characteristics
Three CARMEN isoforms have been annotated - CARMEN1, CARMEN2, and CARMEN3

Found to be a human super enhancer-associated long noncoding RNA controlling cardiac specification differentiation and homeostasis (Ounzain 2015).

Found upstream of MIR-143 and -145 which are two important developmental miRNAs implicated in cardiac precursor specification and differentiation []. This region was shown to harbor a cardiac SRF/NKX2.5-bound enhancer required for cardiac-specific expression of miR-143 and -145 during cardiac development (Xu 2009)

CARMEN is found in a locus encompassed a cardiac super enhancer (Ounzain 2015)

ChIP-analysis demonstrates that these transcripts mapped to a highly active cardiac enhancer (P300) in both fetal and adult human hearts (Ounzain 2015)
Expression
CARMEN1, CARMEN2 and CARMEN3, are found to be at relatively high levels and significantly induced in differentiating fetal cardiac precursor cells (Ounzain 2015)

Expression of CARMEN observed to be negatively correlated to expression of cardiac-specific miR-143 and -145 in differentiating fetal cardiac precursor cells (Ounzain 2015).

In a murine model which uses mouse embryonic stem cells to recapitulates embryonic cardiac development in vitro, Carmen was found to be induced between the cardiac mesoderm and cardiac precursor stages with maximal expression occurring in cardiac precursor. The expression of CARMEN in differentiated cardiomyocytes of the murine model was comparable to the expression in differentiated cardiomyocytes derived from adult mouse heart. The role of CARMEN in cardiac differentiation was also observed in P19CL6 cells (Ounzain 2015)

Carmen expression correlated with enhancer activity high H3K27Ac occupancy levels during cardiac differentiation with maximal enhancer activity occurred between the MES and CPC stages (Ounzain 2015)

Carmen was significantly upregulated post myocardial infarction ( Fig. 8A), supporting a role for Carmen in adult heart homeostasis and cardiac remodeling (Ounzain 2015).

Deregulated expression CARMEN has also been shown in two human heart pathologies, idiopathic dilated cardiomyopathy (DCM) and aortic stenosis (AOS) (Ounzain 2015).
Expression of all three human CARMEN isoforms. CARMEN3 was significantly upregulated in both DCM and AOS whereas CARMEN1 and 2 were only induced in AOS patients (Ounzain 2015)

CARMEN3 expression was markedly higher in post mortem atrium and ventricle heart tissues. CARMEN3. Hypertensive patients demonstrated increased expression of CARM in atria while levels in ventricles was not significantly different (Ounzain 2015)
Function
Relative high expression level in fetal cardiac precursor cells suggest the role of CARMEN in cardiac specification and differentiation (Ounzain 2015)

Cardiogenesis differentiation in P19CL6 cells was blocked when cells are transfected with shRNAi targeting CARMEN. Knockdown of CARMEN expression also resulted in silencing some known cardiogenic regulator including Braveheart (bvht) lncRNA and Mesp1. Consequently, their downstream cardiac TFs Gata4 and Islet1, and the CM-specific genes Myl2, Myh6 were severely inhibited Oct4, Nanog and Emoes expression was also affected by CARMEN knockdown (Ounzain 2015).


In human fetal CPC, antisense-GapmeRs known down of CARMEN resulted in ablation gene expression of cardiac transcription factors and differentiation markers, including GATA4, NKX2.5, TBX5, MYH6, MYH7, and TNNI (Ounzain 2015). CARMEN depletion was associated with decreased expression of the smooth muscle cell marker, MYH11 (Ounzain 2015).. Importantly, CARMEN depletion was not associated with decreased expression of miR-143 and -145, further supporting the notion that CARMEN isoforms are not the precursor transcripts for these miRNAs (Ounzain 2015).. Consequently, CARMEN silencing impaired the capacity of human CPCs to produce differentiated cardiomyocytes., CARMEN-depleted cells were also co-transfected with MIR-143 and MIR-145 mimics were not able to restore cardiogenic differentiation induced by CARMEN knockdown (Ounzain 2015).

Thr cis-acting function of CARMEN was exhibited by the use of a firefly luciferase reporter gene under the control of a basal SV40 promoter inserted downstream of the CARMEN expression cassette (Ounzain 2015).

CARMEN was detected in RNA immunoprecipitation (RIP) assays with antibodies specific to EZH2 and SUZ12, suggesting that Carmen may have trans-repressive roles during cardiac differentiation (Ounzain 2015).
Conservation
A long noncoding RNA, (AK087736), is transcribed from the orthologous region of the mouse genome, which we designate as the mouse ortholog (Ounzain 2015).

The promoter region is highly conserved, supporting an important role in the regulation of transcription at this locus (Ounzain 2015)
Species
Species USCS Genome Browser Link
Homo sapiens (Human) chr5:148,786,442-148,808,241
Mus musculus (Mouse) chr18:61,650,974-61,665,537
Literature
Pub Med ID Author Title Year
26423156 Ounzain CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis. 2015

showing of total 2 results

Associated Components
Component Type Component ID Description Status Pub Med ID
Protein EZHZ RIP confirmed 26423156
Protein SUZ12 RIP confirmed 26423156





lncrnadb version 2.0. lastupdate : 03 Sep 2015