title: DUX4 and DUX4 downstream target genes are expressed in fetal FSHD muscles.
abstract: 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.
authors: INSERM U974, UMR 7215 CNRS, Institut de Myologie, UM 76 Université Pierre et Marie Curie, Paris 75013, France.
authors: Maxime
authors: M
authors: Ferreboeuf
authors: Virginie
authors: V
authors: Mariot
authors: Bettina
authors: B
authors: Bessières
authors: Alexandre
authors: A
authors: Vasiljevic
authors: Tania
authors: T
authors: Attié-Bitach
authors: Sophie
authors: S
authors: Collardeau
authors: Julia
authors: J
authors: Morere
authors: Stéphane
authors: S
authors: Roche
authors: Frédérique
authors: F
authors: Magdinier
authors: Jérôme
authors: J
authors: Robin-Ducellier
authors: Philippe
authors: P
authors: Rameau
authors: Sandra
authors: S
authors: Whalen
authors: Claude
authors: C
authors: Desnuelle
authors: Sabrina
authors: S
authors: Sacconi
authors: Vincent
authors: V
authors: Mouly
authors: Gillian
authors: G
authors: Butler-Browne
authors: Julie
authors: J
authors: Dumonceaux
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000196:embryology* / Q000235:genetics* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D052097:Quadriceps Muscle / Q000196:embryology / Q000378:metabolism; D059368:RNA Isoforms / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064171:Superficial Back Muscles / Q000196:embryology / Q000378:metabolism
chemical_list: C121257:DUX4L1 protein, human; D018398:Homeodomain Proteins; C474632:MBD3L2 protein, human; D020033:Protein Isoforms; D059368:RNA Isoforms; D034741:RNA, Small Interfering; D012097:Repressor Proteins