Genome-Wide Profiling of Peroxisome Proliferator-Activated Receptor γ in Primary Epididymal, Inguinal, and Brown Adipocytes Reveals Depot-Selective Binding Correlated with Gene Expression

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of adipocyte differentiation and function. We and others have previously mapped PPAR gamma 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 PPAR gamma 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 PPAR gamma binding in in vitro differentiated primary mouse adipocytes isolated from epididymal, inguinal, and brown adipose tissues. While these PPAR gamma binding profiles are overall similar, there are clear depot-selective binding sites. Most PPAR gamma binding sites previously mapped in 3T3-L1 adipocytes can also be detected in primary adipocytes, but there are a large number of PPAR gamma 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 PPAR gamma is associated with highly depot-specific gene expression. This indicates that PPAR gamma plays a role in the induction of genes characteristic of different adipocyte lineages and that preadipocytes from different depots are differentially preprogrammed to permit PPAR gamma lineage-specific recruitment even when differentiated in vitro.