UNIGE document Scientific Article
previous document  unige:33562  next document
add to browser collection
Title

Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications

Authors
Coppola, Antonietta
Romito, Antonio
Izzo, Antonella
Altucci, Lucia
show hidden authors show all authors [1 - 12]
Published in Stem Cell Research. 2013, vol. 12, no. 2, p. 323-337
Abstract Understanding the molecular basis of cardiomyocyte development is critical for understanding the pathogenesis of pre- and post-natal cardiac disease. MicroRNAs (miRNAs) are post-transcriptional modulators of gene expression that play an important role in many developmental processes. Here, we show that the miR-99a/let-7c cluster, mapping on human chromosome 21, is involved in the control of cardiomyogenesis by altering epigenetic factors. By perturbing miRNA expression in mouse embryonic stem cells, we find that let-7c promotes cardiomyogenesis by upregulating genes involved in mesoderm specification (T/Bra and Nodal) and cardiac differentiation (Mesp1, Nkx2.5 and Tbx5). The action of let-7c is restricted to the early phase of mesoderm formation at the expense of endoderm and its late activation redirects cells toward other mesodermal derivatives. The Polycomb complex group protein Ezh2 is a direct target of let-7c, which promotes cardiac differentiation by modifying the H3K27me3 marks from the promoters of crucial cardiac transcription factors (Nkx2.5, Mef2c, Tbx5). In contrast, miR-99a represses cardiac differentiation via the nucleosome-remodeling factor Smarca5, attenuating the Nodal/Smad2 signaling. We demonstrated that the identified targets are underexpressed in human Down syndrome fetal heart specimens. By perturbing the expression levels of these miRNAs in embryonic stem cells, we were able to demonstrate that these miRNAs control lineage- and stage-specific transcription factors, working in concert with chromatin modifiers to direct cardiomyogenesis.
Identifiers
PMID: 24365598
Full text
Article (Published version) (2.1 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
Citation
(ISO format)
COPPOLA, Antonietta et al. Cardiomyogenesis is controlled by the miR-99a/let-7c cluster and epigenetic modifications. In: Stem Cell Research, 2013, vol. 12, n° 2, p. 323-337. doi: 10.1016/j.scr.2013.11.008 https://archive-ouverte.unige.ch/unige:33562

459 hits

1 download

Update

Deposited on : 2014-01-22

Export document
Format :
Citation style :