PARP-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the RXR/PPARgamma heterodimer. - Archive ouverte HAL
Article Dans Une Revue Journal of Biological Chemistry Année : 2007

PARP-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the RXR/PPARgamma heterodimer.

Résumé

The peroxisome proliferator activated receptor-g (PPARg, NR1C3) in complex with the retinoid X receptor (RXR) plays a central role in white adipose tissue (WAT) differentiation and function, regulating the expression of key WAT proteins. In this report we show that poly(ADP-ribose) polymerase-2 (PARP-2), also known as an enzyme participating in the surveillance of the genome integrity, is a member of the PPARg/RXR transcription machinery. PARP-2-/- mice accumulate less WAT, characterized by smaller adipocytes. In the WAT of PARP-2-/- mice the expression of a number of PPARg target genes is reduced despite the fact that PPARg1 and g2 are expressed at normal levels. Consistent with this, PARP-2-/- mouse embryonic fibroblasts fail to differentiate to adipocytes. In transient transfection assays, PARP-2 siRNA decreases basal activity and ligand-dependent activation of PPARg, whereas PARP-2 overexpression enhances the basal activity of PPARg, although it does not change the maximal ligand-dependent activation. In addition, we show a DNA-dependent interaction of PARP-2 and PPARg/RXR heterodimer by chromatin immunoprecipitation. In combination, our results suggest that PARP-2 is a novel cofactor of PPARg activity.

Dates et versions

hal-00189730 , version 1 (21-11-2007)

Identifiants

Citer

Péter Bai, Sander M Houten, Aline Huber, Valérie Schreiber, Mitsuhiro Watanabe, et al.. PARP-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the RXR/PPARgamma heterodimer.. Journal of Biological Chemistry, 2007, epub ahead of print. ⟨10.1074/jbc.M701021200⟩. ⟨hal-00189730⟩
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