SNAI1 is upregulated during muscle regeneration and represses FGF21 and ATF3 expression by directly binding their promoters

• DOI: 10.1096/fj.202200215r
• Publication Date: 2022-06-21T09:37:55Z
• Authors: Ines Elia; Giulia Realini; Vittoria Di Mauro; Sara Borghi; Laura Bottoni; Salvatore Tornambè; Libero Vitiello; Stephen J. Weiss; Mario Chiariello; Annalaura Tamburrini; Salvatore Oliviero; Francesco Neri; Maurizio Orlandini; Federico Galvagni
• Keywords: C2C12

During skeletal myogenesis, the zinc-finger transcription factors SNAI1 and SNAI2, are expressed in proliferating myoblasts regulate transition to terminally differentiated myotubes while repressing pro-differentiation genes. Here, we demonstrate that is upregulated vivo during early phase of muscle regeneration induced by bupivacaine injury. Using shRNA-mediated gene silencing C2C12 whole-transcriptome microarray analysis, identified a collection genes belonging endoplasmic reticulum (ER) stress pathway whose expression, myogenic differentiation, was absence SNAI1. Among these, key ER genes, such as Atf3, Ddit3/Chop, Hspa5/Bip, Fgf21, myokine involved were strongly upregulated. Furthermore, promoter mutant analysis Chromatin immune precipitation assay, demonstrated represses Fgf21 Atf3 directly binding multiple E boxes their respective regions. Together, these data describe new regulatory mechanism differentiation involving direct repressive action on ultimately contributing maintaining proliferative undifferentiated state myoblasts.