Researchers in Marseille, in collaboration with a researcher from the Institute of Myology*, have investigated the epigenetic regulation of DUX4 expression—the protein responsible for muscle toxicity in facioscapulohumeral muscular dystrophy (FSHD):
- based on previous observations in embryonic stem cells from mice with FSHD regarding a post-transcriptional regulatory mechanism involving a family of proteins called SUMO (Small Ubiquitin-like Modifiers) that represses the expression of the murine homolog of DUX4,
- similar experiments were conducted in cultures of human muscle affected by FSHD,
- blocking the SUMO pathway (known as SUMOylation) was made possible by using subasumstat, a simple chemical compound,
- all of which led to a reprogramming of the 4q35 locus at the FSHD locus.
The authors believe that the SUMO pathway could represent a new therapeutic target in FSHD.
* Anne Bigot works in the Cellular and molecular orchestration in muscle regeneration, during ageing and in pathologies team at the Center of Research in Myology of the Institute.
