Phosphorylation of the retinoic acid receptor RARgamma2 is crucial for the neuronal differentiation of mouse embryonic stem cells.
Fiche publication
Date publication
mai 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DAVIDSON Irwin, Dr ROCHETTE-EGLY Cécile
Tous les auteurs :
Al Tanoury Z, Gaouar S, Piskunov A, Ye T, Urban S, Jost B, Keime C, Davidson I, Dierich A, Rochette-Egly C
Lien Pubmed
Résumé
Retinoic acid (RA) plays key roles in cell differentiation and growth arrest by activating nuclear RA receptors (RARs) (alpha, beta and gamma), which are ligand-dependent transcription factors. RARs are also phosphorylated in response to RA. Here, we investigated the in vivo relevance of the phosphorylation of RARs during RA-induced neuronal differentiation of mouse embryonic stem cells (mESCs). Using ESCs where the genes encoding each RAR subtype had been inactivated, and stable rescue lines expressing RARs mutated in phospho-acceptor sites, we show that RA-induced neuronal differentiation involves RARgamma2 and requires RARgamma2 phosphorylation. By gene expression profiling, we found that the phosphorylated form of RARgamma2 regulates a small subset of genes through binding an unusual RA response element consisting of two direct repeats with a seven-base-pair spacer. These new findings suggest an important role for RARgamma phosphorylation during cell differentiation and pave the way for further investigations during embryonic development.
Référence
J Cell Sci. 2014 May 1;127(Pt 9):2095-105