Poly(ADP-ribose)polymerase-1 (PARP1) is a chromatin-associated enzyme that was 
described to affect chromatin compaction. Previous reports suggested a dynamic 
modulation of the chromatin landscape during adipocyte differentiation. We thus 
hypothesized that PARP1 plays an important transcriptional role in adipogenesis 
and metabolism and therefore used adipocyte development and function as a model 
to elucidate the molecular action of PARP1 in obesity-related diseases. Our 
results show that PARP1-dependent ADP-ribose polymer (PAR) formation increases 
during adipocyte development and, at late time points of adipogenesis, is 
involved in the sustained expression of PPARγ2 and of PPARγ2 target genes. 
During adipogenesis, PARP1 was recruited to PPARγ2 target genes such as CD36 or 
aP2 in a PAR-dependent manner. Our results also reveal a PAR-dependent decrease 
in repressory histone marks (e.g. H3K9me3) and an increase in stimulatory marks 
(e.g. H3K4me3) at the PPARγ2 promoter, suggesting that PARP1 may exert its 
regulatory function during adipogenesis by altering histone marks. 
Interestingly, activation of PARP1 enzymatic activity was prevented with a 
topoisomerase II inhibitor. These data hint at topoisomerase II-dependent, 
transient, site-specific double-strand DNA breaks as the cause for 
poly(ADP)-ribose formation, adipogenic gene expression, and adipocyte function. 
Together, our study identifies PARP1 as a critical regulator of PPARγ2-dependent 
gene expression with implications in adipocyte function and obesity-related 
disease models.