Non-coding regulation of myogenic chromatin

Advances in sequencing technologies have revealed that more than half of the transcriptome encodes for several classes of RNA molecules lacking coding capacity. The impact of these species on the control of cell growth, differentiation and development, has been well established, and it is clear that they exert their functions in both nuclear and cytoplasmic compartments (Ballarino et al, JCI, 2015). Through RNA-sequencing of murine myoblasts and differentiated myotubes, we recently identified novel long non-coding RNAs (lncRNAs) which expression is dynamically ordered during myogenesis (Ballarino et al, MCB, 2015). These transcripts were classified on the basis of their expression in proliferating versus differentiated conditions, muscle-restricted activation and link with muscle dystrophy. I will describe the characterization of a murine chromatin associated muscle-specific long noncoding RNA, named as Charme (for Chromatin architect of muscle expression), which contributes to the robustness of the myogenic programme both in vitro and in vivo. In myocytes, Charme knock-down produced the disassembly of specific chromosomal domains and the down-regulation of myogenic genes therein contained. Notably, several Charme-affected genes are associated to human cardiomyopathies, and Charme depletion in mice produces a pathologic phenotype consisting in a global alteration of heart architecture. The existence of a homologous human counterpart, which regulates the same subset of genes, suggests an important and evolutionary conserved function for Charme. Altogether, our study identifies a novel example of chromatin-associated lncRNA involved in the acquisition of muscle cell identity