SENP7 deSUMOylase-governed transcriptional program coordinates sarcomere assembly and is targeted in muscle atrophy

Here, we demonstrate that the nuclear role of SENP7 deSUMOylase is pivotal for sarcomere organization. SENP7 expression is temporally upregulated in mature muscle cells and directly regulates transcription of the myosin heavy chain (MyHC-IId) gene.

We identified SENP7-dependent deSUMOylation of Flightless-1 (Fli-I) as a signal for Fli-I association with Scaffold attachment factor b1 (Safb1). SENP7 deficiency led to higher Fli-I SUMOylation and lower chromatin residency of Safb1, thus generating transcriptionally incompetent chromatin conformation on MyHC-IId. Consequently, lower expression of MyHC-IId caused sarcomere disorganization and disrupted muscle cell contraction.