Poly(ADP-ribose) polymerase-2 [corrected] controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/peroxisome proliferator-activated receptor-gamma [corrected] heterodimer.
The peroxisome proliferator-activated receptor-gamma (PPARgamma, 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 PPARgamma/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 PPARgamma target genes is reduced despite the fact that PPARgamma1 and -gamma2 are expressed at normal levels. Consistent with this, PARP-2(-/-) mouse embryonic fibroblasts fail to differentiate to adipocytes. In transient transfection assays, PARP-2 small interference RNA decreases basal activity and ligand-dependent activation of PPARgamma, whereas PARP-2 overexpression enhances the basal activity of PPARgamma, although it does not change the maximal ligand-dependent activation. In addition, we show a DNA-dependent interaction of PARP-2 and PPARgamma/RXR heterodimer by chromatin immunoprecipitation. In combination, our results suggest that PARP-2 is a novel cofactor of PPARgamma activity.
Bai
Péter
P
Département Intégrité du Génome, UMR 7175, CNRS, Ecole Supérieure de Biotechnologie de Strasbourg, BP 10413, Illkirch, France. baip@dote.hu
Houten
Sander M
SM
Huber
Aline
A
Schreiber
Valérie
V
Watanabe
Mitsuhiro
M
Kiss
Borbála
B
de Murcia
Gilbert
G
Auwerx
Johan
J
Ménissier-de Murcia
Josiane
J
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation; D019281:Dimerization; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006579:Heterozygote; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D047495:PPAR gamma / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D047488:Retinoid X Receptors / Q000378:metabolism*
D047495:PPAR gamma; D047488:Retinoid X Receptors; D011065:Poly(ADP-ribose) Polymerases; C459820:Parp2 protein, mouse