Deficiency in the nuclear long noncoding RNA Charme causes myogenic defects and heart remodeling in mice

Abstract

Myogenesis is a highly regulated process that involves the conversion of progenitor cells into multinucleated myofibers. Besides proteins and mi RNAs, long noncoding RNAs (lnc RNAs) have been shown to participate in myogenic regulatory circuitries. Here, we characterize a murine chromatin‐associated muscle‐specific lnc RNA, Charme, which contributes to the robustness of the myogenic program in vitro and in vivo. In myocytes, Charme depletion triggers the disassembly of a specific chromosomal domain and the downregulation of myogenic genes contained therein. Notably, several Charme‐sensitive genes are associated with human cardiomyopathies and Charme depletion in mice results in a peculiar cardiac remodeling phenotype with changes in size, structure, and shape of the heart. Moreover, the existence of an orthologous transcript in human, regulating the same subset of target genes, suggests an important and evolutionarily conserved function for Charme. Altogether, these data describe a new example of a chromatin‐associated lnc RNA regulating the robustness of skeletal and cardiac myogenesis.