Fiche publication
Date publication
décembre 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr COIN Frédéric
,
Dr EGLY Jean-Marc
,
Dr SCHREIBER Valérie
Tous les auteurs :
Le May N, Iltis I, Ame JC, Zhovmer A, Biard D, Egly JM, Schreiber V, Coin F
Lien Pubmed
Résumé
Poly-(ADP-ribose) glycohydrolase (PARG) is a catabolic enzyme that cleaves ADP-ribose polymers synthesized by poly-(ADP-ribose) polymerases. Here, transcriptome profiling and differentiation assay revealed a requirement of PARG for retinoic acid receptor (RAR)-mediated transcription. Mechanistically, PARG accumulates early at promoters of RAR-responsive genes upon retinoic acid treatment to promote the formation of an appropriate chromatin environment suitable for transcription. Silencing of PARG or knockout of its enzymatic activity maintains the H3K9me2 mark at the promoter of the RAR-dependent genes, leading to the absence of preinitiation complex formation. In the absence of PARG, we found that the H3K9 demethylase KDM4D/JMJD2D became PARsylated. Mutation of two glutamic acids located in the Jumonji N domain of KDM4D inhibited PARsylation. PARG becomes dispensable for ligand-dependent transcription when either a PARP inhibitor or a non-PARsylable KDM4D/JMJD2D mutant is used. Our results define PARG as a coactivator regulating chromatin remodeling during RA-dependent gene expression.
Référence
Mol Cell. 2012 Dec 14;48(5):785-98
