SENP7 deSUMOylase-governed transcriptional program coordinates sarcomere assembly and is targeted in muscle atrophy.
Cell Rep
; 41(8): 111702, 2022 11 22.
Article
in En
| MEDLINE
| ID: mdl-36417853
ABSTRACT
Disorganization of the basic contractile unit of muscle cells, i.e., the sarcomeres, leads to suboptimal force generation and is a hallmark of 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 identify SENP7-dependent deSUMOylation of flightless-1 (Fli-I) as a signal for Fli-I association with scaffold attachment factor b1 (Safb1). SENP7 deficiency leads 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 causes sarcomere disorganization and disrupted muscle cell contraction. Remarkably, cachexia signaling impedes the SENP7-governed transcriptional program, leading to muscle atrophy, with profound loss of motor protein MyHC-IId. We propose a SENP7-driven distinct transcription program as paramount for muscle cell function, which was found targeted in cachexia.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sarcomeres
/
Cachexia
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2022
Type:
Article
Affiliation country:
Germany