Chromatin Accessibility and Transcription Factor Binding at the PPAR gamma 2 Promoter During Adipogenesis is Protein Kinase A-Dependent

The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor that specifies formation of the adipocyte lineage. PPAR gamma also serves as a primary target for the treatment of type 2 diabetes, illustrating both its medical relevance as well as the need to understand fundamental aspects of PPAR gamma expression and function. Here, we characterize molecular changes that occur at the PPAR gamma 2 promoter within the first several hours of adipocyte differentiation in culture. Our results demonstrate that changes in chromatin accessibility at the PPAR gamma 2 promoter and occupancy of the promoter by the c-Fos transcription factor occur within an hour of the onset of differentiation, followed closely by the binding of the CCAAT/ enhancer binding protein beta (C/EBPb) transcription factor. All three events show a remarkable dependency on protein kinase A(PKA) activity. These results reflect novel requirements for the PKA signaling pathway and reinforce the importance of PKA function during the onset of adipocyte differentiation. J. Cell. Physiol. 226: 86-93, 2010. (C) 2010 Wiley-Liss, Inc.