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2014-07-06 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Lancelot Céline, Ansseau Eugénie , Tassin Alexandra , Matteoti Christel, Leroy Baptiste , Gerbaux Cécile, Zorbo Sabrina, Cloet Samuel, Yip Cassandre, Laoudj-Chenivesse Dalila, Wattiez Ruddy , Belayew Alexandra , Coppée Frédérique , "Study of the double homeodomain DUX protein partners: focus on the interaction with desmin." in IF-NMD Workshop Nice 2014 - Satellite Workshop to ICNMD, Nice, France, 2014

  • Codes CREF : Pathologies particulières (DI3370)
  • Unités de recherche UMONS : Biochimie métabolique et moléculaire (M122)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)
  • Centres UMONS : Mind & Health (CREMH)

Abstract(s) :

(Anglais) Study of the double homeodomain DUX protein partners: focus on the interaction with desmin. Alexandra Tassin, Eugénie Ansseau, Christel Matteotti, Céline Lancelot, Baptiste Leroy, Cécile Gerbaux, Sabrina Zorbo, Samuel Cloet, Cassandre Yip, Dalila Laoudj-Chenivesse, Ruddy Wattiez, Alexandra Belayew and Frédérique Coppée. Abstract The DUX (double homeobox) family comprises hundreds of genes that map within repeated elements dispersed in the human genome. Only a dozen DUX genes have been fully sequenced to this date and found to present highly similar and very GC-rich sequences. Even if the evolutionary conservation of their sequences argues in favor of a functionality, they were long considered as pseudogenes. Our group has characterized the DUX4 genes mapped in the D4Z4 repeat array in 4q35 and contributed to demonstrate a causal role in the FSHD muscular dystrophy. The DUX4 protein can specifically interact with DNA and is a potent transcriptional activator. In the present study we further investigated the functions of proteins encoded by genes we had identified: DUX1 that is limited to the double homeodomain, DUX4 and DUX4c that only differ in their carboxy-terminal extension. We first used the yeast two-hybrid system to screen an adult human skeletal muscle cDNA library with DUX1 or DUX4c that presented no or weak transcriptional activity in this system. We also expressed Halo-tag-DUX4 or DUX4c fusion proteins in human muscle cells, co-purified them by affinity chromatography with their protein partners and identified these by mass spectrometry. Some partners intriguingly belonged to cytoplasmic intermediate filaments and the most frequent of these was desmin for DUX1 and DUX4c. We confirmed these interactions by in vitro GST pull down and co-immunoprecipitations. We also confirmed desmin interaction with DUX4c in control muscle cells and with DUX4 or DUX4c in pathological muscle cells by in situ proximal ligation assay. Moreover, DUX4c and desmin immunostaining partially co-localized in transversal sections of a muscle obtained from a patient affected with Duchenne Muscular Dystrophy. The DUX4c staining was found either in the nuclei or in the sarcoplasm of many regenerative fibres exhibiting a higher intracellular desmin labelling. This observation confirmed previous data suggesting a role of DUX4c during muscle regeneration. DUX4c could therefore be considered as a new marker of human muscle regeneration.