title: Loss of function of myosin chaperones triggers Hsf1-mediated transcriptional response in skeletal muscle cells.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Campus Nord, PO box, Karlsruhe, Germany.
authors.forename: Christelle
authors.initials: C
authors.lastname: Etard
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Campus Nord, PO box, Karlsruhe, Germany.
authors.forename: Olivier
authors.initials: O
authors.lastname: Armant
authors.affiliation: Present address: Institute of Inflammation and Repair, Michael Smith Bldg, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
authors.forename: Urmas
authors.initials: U
authors.lastname: Roostalu
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Campus Nord, PO box, Karlsruhe, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Gourain
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Campus Nord, PO box, Karlsruhe, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Ferg
authors.affiliation: Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Campus Nord, PO box, Karlsruhe, Germany. uwe.straehle@kit.edu.
authors.forename: Uwe
authors.initials: U
authors.lastname: Strähle
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D009124:Muscle Proteins; C472790:Unc45b protein, zebrafish; D029961:Zebrafish Proteins; D011495:Histone-Lysine N-Methyltransferase; C510871:SmyD1a protein, zebrafish; D009218:Myosins