DUX4 and DUX4 downstream target genes are expressed in fetal FSHD muscles
| Autor: | Sophie Collardeau, Julia Morere, Virginie Mariot, Stéphane Roche, Vincent Mouly, Julie Dumonceaux, Sandra Whalen, Frédérique Magdinier, Bettina Bessières, Philippe Rameau, Alexandre Vasiljevic, Tania Attié-Bitach, Claude Desnuelle, Jérôme Robin-Ducellier, Gillian Butler-Browne, Maxime Ferreboeuf, Sabrina Sacconi |
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| Přispěvatelé: | Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), RUIZ, Caroline |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology DUX4 Muscle Fibers Skeletal Muscle Development [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Quadriceps Muscle 0302 clinical medicine RNA Isoforms Protein Isoforms Facioscapulohumeral muscular dystrophy RNA Small Interfering Muscular dystrophy [SDV.BDD]Life Sciences [q-bio]/Development Biology Cells Cultured Genetics (clinical) Regulation of gene expression 0303 health sciences medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Myogenesis Gene Expression Regulation Developmental General Medicine Middle Aged Muscular Dystrophy Facioscapulohumeral 3. Good health [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Muscle Female Adult Gene isoform medicine.medical_specialty Biology 03 medical and health sciences Fetus [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] [SDV.BDD] Life Sciences [q-bio]/Development Biology Biopsy Genetics medicine Humans Molecular Biology 030304 developmental biology Homeodomain Proteins FSHD Molecular markers [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Biomarker medicine.disease Molecular biology Repressor Proteins Superficial Back Muscles 030217 neurology & neurosurgery |
| Zdroj: | Human Molecular Genetics Human Molecular Genetics, Oxford University Press (OUP), 2013, 23 (1), epub ahead of print. ⟨10.1093/hmg/ddt409⟩ Human Molecular Genetics, 2013, 23 (1), epub ahead of print. ⟨10.1093/hmg/ddt409⟩ |
| ISSN: | 0964-6906 1460-2083 |
| Popis: | International audience; : 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. |
| Databáze: | OpenAIRE |
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