The DUX4 gene at the FSHD1A locus encodes a pro-apoptotic protein
| Autor: | E. Daniel Corona, Alexandra Belayew, Eugénie Ansseau, Denise A. Figlewicz, Dalila Laoudj-Chenivesse, Cristina Arias, Nicolás Gonzalo Núñez, Ruddy Wattiez, Sébastien Sauvage, Valeria Kowaljow, Christel Matteotti, Oberdan Leo, Cecilia Conde, Alberto L. Rosa, Aline Marcowycz, Frédérique Coppée |
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| Přispěvatelé: | MORNET, Dominique, Instituto de Investigación Médica Mercedes y Martín Ferreyra [Córdoba] (INIMEC), Universidad Nacional de Córdoba [Argentina]-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Université de Mons-Hainaut, Université libre de Bruxelles (ULB), University of Michigan [Ann Arbor], University of Michigan System, Muscle et pathologies, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2007 |
| Předmět: |
musculoskeletal diseases
congenital hereditary and neonatal diseases and abnormalities Transcription Genetic DUX4 Nuclear Envelope [SDV]Life Sciences [q-bio] Molecular Sequence Data Emerin Gene Expression Apoptosis Biology Quadriceps Muscle Cell Line Tumor Rhabdomyosarcoma medicine Homeobox Facioscapulohumeral muscular dystrophy Humans Amino Acid Sequence RNA Messenger Gene Genetics (clinical) Homeodomain Proteins FSHD Muscle Cells Expression vector Membrane Proteins Nuclear Proteins Transfection medicine.disease Molecular biology Muscular Dystrophy Facioscapulohumeral Chromatin [SDV] Life Sciences [q-bio] Neurology Cell culture Pediatrics Perinatology and Child Health Muscle Neurology (clinical) |
| Zdroj: | Neuromuscular Disorders Neuromuscular Disorders, 2007, 17 (8), pp.611-623. ⟨10.1016/j.nmd.2007.04.002⟩ |
| ISSN: | 0960-8966 |
| DOI: | 10.1016/j.nmd.2007.04.002⟩ |
| Popis: | International audience; Facioscapulohumeral muscular dystrophy (FSHD) patients carry contractions of the D4Z4-tandem repeat array on chromosome 4q35. Decrease in D4Z4 copy number is thought to alter a chromatin structure and activate expression of neighboring genes. D4Z4 contains a putative double-homeobox gene called DUX4. We identified DUX4 mRNAs in cells transfected with genomic fragments containing the DUX4 gene. Using RT-PCR we also recognized expressed DUX4 mRNAs in primary FSHD myoblasts. Polyclonal antibodies raised against specific DUX4 peptides detected the DUX4 protein in cells transfected with D4Z4 elements. DUX4 localizes in the nucleus of cells transfected with CMV–DUX4 expression vectors. A DUX4-related protein is endogenously expressed in nuclei of adult and fetal human rhabdomyosarcoma cell lines. Overexpression of DUX4 induces cell death, induces caspase 3/7 activity and alters emerin distribution at the nuclear envelope. We propose that DUX4-mediated cell death contributes to the pathogenic pathway in FSHD. |
| Databáze: | OpenAIRE |
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