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2008-05-26 - Colloque/Présentation - poster - Anglais - 1 page(s)

Tassin Alexandra , Vanderplanck Céline, Ansseau Eugénie , Marcowyzc Aline, Barro Marietta, Laoudj-Chenivesse Dalila, Belayew Alexandra , Coppée Frédérique , "Studies on the expression and function of DUX4c, a gene located close to the FSHD locus" in 3ème Congrès International de Myologie, Marseille, France, 2008

  • 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 disease linked to contractions of a repeat array in the 4q35 subtelomeric region. In non-affected individuals the array comprises 11-100 tandem copies of a 3.3-kb element named D4Z4 in which we have identified the DUX4 double homeobox gene. The FSHD deletions reduce the D4Z4/DUX4 copy numbers to between 1 and 10, and activate genes in the vicinity by chromatin loop alterations. We have shown that DUX4 was activated and played a major role in FSHD. We now focus on a homologous gene (DUX4c) mapped 42 kb centromeric of the repeat array. The DUX4c mRNA and protein were expressed in control human primary myoblasts. The protein was observed in nuclei by immunofluorescence with a specific antiserum, and it was induced upon differentiation to myotubes. The protein level detected by Western blot increased 1.5-2-fold in FSHD versus control or DMD (Duchenne Muscular dystrophy) myotubes. It was also induced in FSHD (2-10-fold) and in DMD (3-4-fold) muscle biopsies as compared to controls. The increase in DMD samples might result from the multiple muscle degeneration/regeneration cycles characteristic of the disease. In a functional study we transfected human TE671 rhabdomyosarcoma cells with pCINeo expression vectors for either DUX4, DUX4c, DUX1 or without insert. We observed a strong up-regulation of PCNA (proliferating cell nuclear antigen) 24h post-transfection in DUX4c expressing cells only. These cells continued to proliferate in differentiation medium instead of aligning to fuse into myotubes like the other transfected cells. Since DUX4c specifically induced the MYF5 transcription factor, these findings suggested a role in muscle regeneration not restricted to FSHD. We propose that as well an excess (in FSHD patients) as a reduced amount (in families where the D4Z4 deletion removes the DUX4c gene) of DUX4c expression could affect muscle regeneration and contribute to the FSHD pathology.