The Trithorax protein Ash1L promotes myoblast fusion by activating Cdon expression.
Ilaria CastiglioniRoberta CacciaJose Manuel Garcia-ManteigaGiulia FerriGiuseppina CarettiIvan MolinerisKenichi NishiokaDavide GabelliniPublished in: Nature communications (2018)
Myoblast fusion (MF) is required for muscle growth and repair, and its alteration contributes to muscle diseases. The mechanisms governing this process are incompletely understood, and no epigenetic regulator has been previously described. Ash1L is an epigenetic activator belonging to the Trithorax group of proteins and is involved in FSHD muscular dystrophy, autism and cancer. Its physiological role in skeletal muscle is unknown. Here we report that Ash1L expression is positively correlated with MF and reduced in Duchenne muscular dystrophy. In vivo, ex vivo and in vitro experiments support a selective and evolutionary conserved requirement for Ash1L in MF. RNA- and ChIP-sequencing indicate that Ash1L is required to counteract Polycomb repressive activity to allow activation of selected myogenesis genes, in particular the key MF gene Cdon. Our results promote Ash1L as an important epigenetic regulator of MF and suggest that its activity could be targeted to improve cell therapy for muscle diseases.
Keyphrases
- municipal solid waste
- skeletal muscle
- sewage sludge
- duchenne muscular dystrophy
- muscular dystrophy
- dna methylation
- genome wide
- poor prognosis
- gene expression
- transcription factor
- single cell
- binding protein
- anaerobic digestion
- signaling pathway
- insulin resistance
- autism spectrum disorder
- metabolic syndrome
- papillary thyroid
- genome wide identification
- copy number
- cell therapy
- high throughput
- long non coding rna
- immune response
- adipose tissue
- protein protein
- mesenchymal stem cells
- lymph node metastasis
- squamous cell
- bone marrow
- inflammatory response
- nucleic acid