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Article Dans Une Revue Human Molecular Genetics Année : 2013

DUX4 and DUX4 downstream target genes are expressed in fetal FSHD muscles.

Maxime Ferreboeuf
  • Fonction : Auteur
Virginie Mariot
  • Fonction : Auteur
Bettina Bessières
  • Fonction : Auteur
Alexandre Vasiljevic
  • Fonction : Auteur
Tania Attié-Bitach
  • Fonction : Auteur
Sophie Collardeau
  • Fonction : Auteur
Jérôme Robin-Ducellier
Philippe Rameau
  • Fonction : Auteur
Sandra Whalen
Vincent Mouly
Gillian Butler-Browne
Julie Dumonceaux
  • Fonction : Auteur

Résumé

: Facioscapulohumeral muscular dystrophy (FSHD) is one of the most prevalent adult muscular dystrophies. The common clinical signs usually appear during the second decade of life but when the first molecular dysregulations occur is still unknown. Our aim was to determine whether molecular dysregulations can be identified during FSHD fetal muscle development. We compared muscle biopsies derived from FSHD1 fetuses and the cells derived from some of these biopsies with biopsies and cells derived from control fetuses. We mainly focus on DUX4 isoform expression because the expression of DUX4 has been confirmed in both FSHD cells and biopsies by several laboratories. We measured DUX4 isoform expression by using qRT-PCR in fetal FSHD1 myotubes treated or not with an shRNA directed against DUX4 mRNA. We also analyzed DUX4 downstream target gene expression in myotubes and fetal or adult FSHD1 and control quadriceps biopsies. We show that both DUX4-FL isoforms are already expressed in FSHD1 myotubes. Interestingly, DUX4-FL expression level is much lower in trapezius than in quadriceps myotubes, which is confirmed by the level of expression of DUX4 downstream genes. We observed that TRIM43 and MBD3L2 are already overexpressed in FSHD1 fetal quadriceps biopsies, at similar levels to those observed in adult FSHD1 quadriceps biopsies. These results indicate that molecular markers of the disease are already expressed during fetal life, thus opening a new field of investigation for mechanisms leading to FSHD.
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Dates et versions

hal-00868855 , version 1 (18-12-2017)

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Maxime Ferreboeuf, Virginie Mariot, Bettina Bessières, Alexandre Vasiljevic, Tania Attié-Bitach, et al.. DUX4 and DUX4 downstream target genes are expressed in fetal FSHD muscles.. Human Molecular Genetics, 2013, 23 (1), epub ahead of print. ⟨10.1093/hmg/ddt409⟩. ⟨hal-00868855⟩
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