Gene Expression and muscular dystrophy

Dulbecco Telethon Institute - ERC Starting Grant
Davide Gabellini, Head of Unit

Although most cells contain an identical set of genes, they can be extremely diverse in appearance and function. It is the selective expression and repression of genes that determines the specific properties of individual cells. Maintenance of the correct gene expression pattern is fundamental for organism integrity. For this reason, failure to repress genes appropriately has been connected to many human diseases. An important example of a genetic disorder associated to transcriptional imbalance is facioscapulohumeral muscular dystrophy (FSHD). FSHD is one of the most common hereditary diseases of muscle. Unlike the majority of genetic diseases, FSHD is not due to a classical mutation within a protein-coding gene. Our results suggest that FSHD is due to an epigenetic alteration causing over-expression of the gene FRG1. Accordingly, transgenic mice over-expressing FRG1 develop an FSHD phenotype and represent the first animal model of the disease. Our group is interested in elucidating the role of the epigenome in shaping the skeletal muscle and in the pathogenesis of muscular dystrophy. We are using the FSHD animal model to understand the molecular pathogenesis of FSHD and test possible therapeutic approaches.