ZFIN ID: ZDB-PUB-151204-6
Loss of function of myosin chaperones triggers Hsf1-mediated transcriptional response in skeletal muscle cells
Etard, C., Armant, O., Roostalu, U., Gourain, V., Ferg, M., Strähle, U.
Date: 2015
Source: Genome biology   16: 267 (Journal)
Registered Authors: Armant, Olivier, Etard, Christelle, Ferg, Marco, Gourain, Victor, Roostalu, Urmas, Strähle, Uwe
Keywords: none
Microarrays: GEO:GSE74202
MeSH Terms:
  • Animals
  • Disease Models, Animal
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • HSP90 Heat-Shock Proteins/biosynthesis
  • HSP90 Heat-Shock Proteins/genetics*
  • Histone-Lysine N-Methyltransferase/biosynthesis
  • Histone-Lysine N-Methyltransferase/genetics*
  • Humans
  • Molecular Chaperones/biosynthesis
  • Molecular Chaperones/genetics*
  • Muscle, Skeletal/growth & development
  • Muscle, Skeletal/metabolism
  • Muscular Diseases/genetics*
  • Muscular Diseases/metabolism
  • Muscular Diseases/pathology
  • Mutation
  • Myosins/genetics*
  • Myosins/metabolism
  • Protein Binding
  • Protein Folding
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics*
PubMed: 26631063 Full text @ Genome Biol.
Mutations in myosin chaperones Unc45b and Hsp90aa1.1 as well as in the Unc45b-binding protein Smyd1b impair formation of myofibrils in skeletal muscle and lead to the accumulation of misfolded myosin. The concomitant transcriptional response involves up-regulation of the three genes encoding these proteins, as well as genes involved in muscle development. The transcriptional up-regulation of unc45b, hsp90aa1.1 and smyd1b is specific to zebrafish mutants with myosin folding defects, and is not triggered in other zebrafish myopathy models.
By dissecting the promoter of unc45b, we identify a Heat shock factor 1 (Hsf1) binding element as a mediator of unc45b up-regulation in myofibers lacking myosin folding proteins. Loss-of-function of Hsf1 abolishes unc45b up-regulation in mutants with defects in myosin folding.
Taken together, our data show that skeletal muscle cells respond to defective myosin chaperones with a complex gene program and suggest that this response is mediated by Hsf1 activation.