PPARγ and the global map of adipogenesis and beyond

• PPARγ is directly involved in regulating the majority of adipocyte genes.
• Binding of PPARγ to genomic targets depends on cooperating transcription factors.
• Cell type-specific programming of the chromatin landscape determines PPARγ binding.
• Regulatory networks of PPARγ are evolutionarily conserved but binding sites are not.

Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors (TFs) and function as a master regulator of adipocyte differentiation and metabolism. We review recent breakthroughs in the understanding of PPARγ gene regulation and function in the chromatin context. It is now clear that multiple TFs team up to induce PPARγ during adipogenesis, and that other TFs cooperate with PPARγ to ensure adipocyte-specific genomic binding and function. We discuss how this differs in other PPARγ-expressing cells such as macrophages and how these genome-wide mechanisms are preserved across species despite modest conservation of specific binding sites. These emerging considerations inform our understanding of PPARγ function as well as of adipocyte development and physiology.