A TRANSLATIONAL APPROACH ON RARE CHROMATIN DISORDERS
Mardi 12 février 2019 11:00
- Duree : 1 heure
Lieu : Salle de Conférence de l’IAB - Rond Point de La Chantourne, 38700 La Tronche (arrêt de tram Grand Sablon, ligne B)
Orateur : Julien THEVENON (CHU, Grenoble)
The causes of ultra-rare developmental disorders remains to be fully defined. Chromatin regulatory mechanisms maintain cellular identity and function, where misregulation may lead to developmental defects. In this work, we report pathogenic mutations of a chromatin protein,
named MSL3 and which encodes a member of the chromatin-associated male-specific lethal (MSL). The MSL complex is an histone acetyl transferase which is responsible for bulk histone H4 lysine 16 acetylation (H4K16ac) in flies and mammals. Genetic mutations in MSL3 cause an X-linked syndrome affecting both sexes. Clinical features of the syndrome include developmental delay and recognizable facial dysmorphism. We show that MSL3 mutations affect MSL complex assembly and activity and is accompanied by a pronounced loss of H4K16ac levels. Patient-derived cells display global transcriptome alterations of pathways involved in morphogenesis and cell migration. Finally, histone deacetylase inhibitors can rebalance acetylation levels and alleviate some of the molecular and cellular phenotypes of patient cells. Taken together, we characterize a syndrome that allowed us to decipher the developmental importance of MSL3 in humans.
Contact : karin.sadoul@univ-grenoble-alpes.fr
Discipline évènement : (Biologie / Chimie)
Entité organisatrice : (IAB)
Nature évènement : (Séminaire)
Evènement répétitif : (Mardis de l’IAB)
Site de l'évènement : Pôle Santé / La Tronche
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