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DUPRET Barbara (INSERM U908 - Pierre-Olivier ANGRAND)
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@mail :  pierre-olivier.angrand@univ-lille1.fr      tél. :

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Titre de la communication :
Application of the TALEN methodology in zebrafish to study the Polycomb Repression
Auteurs (et leurs adresses) de la communication :
Barbara DUPRET 1, Pamela VÖLKEL 1,2, Constance VENNIN 1,3, Xuefen LE BOURHIS 1, Pierre-Olivier ANGRAND 1 1 Plasticité Cellulaire & Cancer - U908 Inserm / Université de Lille1, 59655 Villeneuve d'Ascq, France. 2 CNRS 3 SIRIC ONCOLille
Résumé de la communication :
In eukaryotes, post-translational modifications of histone proteins play a crucial role in chromatin organization and in the control of gene expression programs. Polycomb group (PcG) proteins are part of the enzymatic machineries involved in these histone modifications. PcG proteins interact to form two major multiprotein complexes, Polycomb Repressive Complex 1 (PRC1) and PRC2 which catalyze two post-translational histone modifications involved in chromatin compaction and gene silencing. PRC1 is responsible for monoubiquitinylation of histone H2A at lysine 119 (H2AK119ub1) whereas PRC2 trimethylates lysine 27 of histone H3 (H3K27me3) allowing the recruitment of PRC1.
To gain insights into the Polycomb repression in vertebrates, we applied a genetic approach. Using the TALEN technology, we engineered zebrafish (Danio rerio) harboring mutations in the pcgf1 and ezh2 Polycomb genes. Pcgf1 is a subunit of the PRC1 complex whereas Ezh2 is the histone lysine methyltransferase of the PRC2 complex.
Mutant pcgf1-/- fish are viable and fertile, but the growth rate at early developmental stages is reduced in absence of pcgf1 gene function and a significant number of pcgf1-/- fish show signs of premature aging.
In contrast, ezh2-/- zebrafish die at 12 days post-fertilization (dpf) with alterations of the intestine wall. Analyses of mutant zebrafish reveal that the intestine formation is normal at 5 dpf but its integrity is lost at 11 dpf indicating that Ezh2 is essential for tissue maintenance but not for tissue formation.
Altogether, our results highlight a link between epigenetics and aging and tissue maintenance.

DUPRET Barbara (INSERM U908 - Pierre-Olivier ANGRAND)