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2005-05-09 - Colloque/Présentation - poster - Anglais - 1 page(s)

Ansseau Eugénie , Sauvage Sébastien, Laoudj-Chenivesse Dalila, Carnac G, Marcowycz Aline, Leroy Axelle, Leclercq India, Figlewicz Denise, Belayew Alexandra , Coppée Frédérique , "Characterization of DUX4c, a double homeobox gene located in a truncated and inverted D4Z4 element, and its expression in FSHD mlyoblasts" in Congrès Myologie 2005, Nantes, France, 2005

  • Codes CREF : Biologie moléculaire (DI3111), Pathologies particulières (DI3370)
  • Unités de recherche UMONS : Biologie moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)

Abstract(s) :

(Anglais) Facioscapulohumeral muscular dystrophy (FSHD) is a dominant condition linked to partial deletions in a stretch of 3.3-kb repeated elements named D4Z4 in the 4q35 subtelomeric region. These deletions are thought to alter local chromatin structure and allow transcriptional activation of neighbouring genes, several of which have been characterized. We previously identified a putative double homeobox (DUX4) gene within the D4Z4 unit itself. In the present study, we characterized the homologous DUX4c gene in an isolated D4Z4 unit mapping 42 kb centromeric of the D4Z4 repeat array. DUX4c differed from DUX4 in the promoter region, and by the presence of a putative polyadenylation signal. The open reading frame (ORF) encoded a 374-residue protein highly similar to DUX4 except in its shorter carboxyl-terminal domain. The DUX4c promoter drove transient expression of a linked luciferase gene in muscle cells. RNA’s encompassing its ORF were detected in cells transfected with the DUX4c natural gene. 5’RACE experiments identified multiple transcription initiation sites next to GC boxes, upstream from the start codon. 3’RACE experiments showed alternative splicing downstream of the STOP codon. A rabbit antiserum raised against a DUX4c-specific peptide detected a 47 kDa protein on a Western blot prepared with nuclear extracts of cells transfected with a DUX4c expression vector. Such a protein was also detected in FSHD myoblasts and in some FSHD but not control muscle biopsies. Its expression was induced following myoblast differentiation. In conclusion, our data demonstrated that the DUX4c gene was functional and expressed in FSHD myoblasts. However a deletion extending from the D4Z4 repeat array to DUX4c was found in two families with FSHD (Lemmers et al, 2003, Neurology 22, 178-83), suggesting that it does not causing the disease. DUX4c is nevertheless present in most patients and could influence the variable FSHD phenotype.