Chemical inhibition of SUMOylation activates the FSHD locus

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 locusPosition d’un gène dans le génome. Le locus d’un gène est désigné par le numéro du chromosome, le bras du chromosome, puis sa place. Par exemple le gène de la maladie de Duchenne est sur le locus Xp21, ce qui veut dire qu’il est sur le locus 21 du bras court (p) du chromosome X. 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.

Chemical inhibition of SUMOylation activates the FSHD locus. Nordlinger A, Morin L, Andrieux A, Trani JP, Perrin P, Eudes N, Bigot A, Dejean A, Magdinier F. Sci Rep. 2026 Jan