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3ABrD : un nouveau facteur d'organisation de l'épigénome associé au cancer

Thématique(s) :
Génomique fonctionnelle

Responsable(s) :

CARON Cécile


Institution(s) :

Biologie moléculaire et cellulaire de la différenciation U309 (INSERM)

Résumé :

The present project is developed in the context of the « EpiPro » (Epigenetic Profiling) program coordinated by E. Gilson and S. Khochbin and recently funded by INCa/CLARA. Within this collaborative network, our team is particularly interested in the study of bromodomain-containing proteins likely to be involved in establishing and reading the epigenetic information related to acetylated chromatin, and found deregulated in cancers. Recently, an in silico search for new bromodomain-containing factors deregulated in cancers led us to focus on a completely unknown protein, which interestingly associates a bromodomain (a module of binding to acetylated proteins) to a chaperone activity of the AAATPase family, which we named 3ABrD. We started a project aiming to functionally characterize this protein and to analyse its expression in tissues and tumours. Several powerful tools have already been developed, including expression vectors encoding wild type or inactive mutants of 3ABrD, antibodies, siRNA inducing its very efficient knock-down, and RT-qPCR analyses. The first data obtained clearly show an up-regulation of 3ABrD in transformed cell lines and in tumours, and strongly argue for its action as an epigenomic organizer specifically targeting chromatin acetylated on histone H4. These promising results highly suggest that the up-regulation and/or the dysfunction of 3ABrD could disturb the acetylation-dependant functions of the epigenome, and thus participate in the process of oncogenesis or tumorigenesis. Hence, new questions arise from our work on 3ABrD, which has essentially been performed by a PhD student now at the end of her stay. The purpose of the present postdoctoral research project is now to answer these new questions concerning the exact nature of the epigenome functions regulated by 3ABrD, and its mechanism of action. The proposed approaches are 1/ the identification of 3ABrD partners by a purification of its complex from cell extracts 2/ the study of the action of 3ABrD on acetylated chromatin by in vitro chromatin remodeling assays, and 3/ functional studies on living cells to test the potential roles of 3ABrD and its partners deduced from the previous results.


Rencontres "Industriels - Académiques" du CLARA - 1er octobre 2008
(Rubrique)
Symposium Axe IV "Epidémiologie des Cancers, SHS et éducation du patient" - 17-18 décembre 2008
(Rubrique)
Joint Meeting CLARA – DKFZ – CGE on Infections & Cancer - 23-24 janvier 2009
(Rubrique)
Résultats des Appels à Projet INCa - Février 2008
(Fichier)
Preuve du Concept
(Rubrique)
Rapport d'activités 2007 du CLARA
(Actualité)
Liste des équipes académiques et cliniques du CLARA
(Actualité)
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