Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation and function. We and others have previously mapped PPARγ binding at a genome-wide level in murine and human adipocyte cell lines and in primary human adipocytes. However, little is known about how binding patterns of PPARγ differ between brown and white adipocytes and among different types of white adipocytes. Here we have employed chromatin immunoprecipitation combined with deep sequencing to map and compare PPARγ binding in in vitro differentiated primary mouse adipocytes isolated from epididymal, inguinal, and brown adipose tissues. While these PPARγ binding profiles are overall similar, there are clear depot-selective binding sites. Most PPARγ binding sites previously mapped in 3T3-L1 adipocytes can also be detected in primary adipocytes, but there are a large number of PPARγ binding sites that are specific to the primary cells, and these tend to be located in closed chromatin regions in 3T3-L1 adipocytes. The depot-selective binding of PPARγ is associated with highly depot-specific gene expression. This indicates that PPARγ plays a role in the induction of genes characteristic of different adipocyte lineages and that preadipocytes from different depots are differentially preprogrammed to permit PPARγ lineage-specific recruitment even when differentiated in vitro.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00526-12.
ACKNOWLEDGMENTS
We thank the members of the Mandrup laboratory for fruitful discussions and the Lazar laboratory for input to the development of ChIP protocol for adipose tissue. Rosiglitazone was a kind gift from Per Sauerberg, Novo Nordisk A/S.
This work has been supported in part by grants from the Lundbeck Foundation, the Novo Nordisk Foundation, the Danish Independent Research Council Natural Sciences, and the Swedish Research Council and by grants from NordForsk given to the Nordic Centre of Excellence MitoHealth.