DNA Bending Is Induced by Binding of the Peroxisome Proliferator-Activated Receptor γ2 Heterodimer to Its Response Element in the Murine Lipoprotein Lipase Promoter

Abstract The peroxisome proliferator activated receptor γ2 (PPARγ2) is a critical transcriptioinal regulator of adipogenesis. Lipoprotein lipase is one of the earliest genes induced following exposure of pre-adipocytes to PPARγ2 ligands such as the thiazolidinediones. A unique PPARγ2 DNA recognition element was mapped to the region between −171 to −149 bp of the murine LPL promoter, based on transfection analysis of deletion constructs and gel retention assays using bacterially expressed, affinity purified recombinant proteins. Circular permutation analysis determined that binding of the PPARγ2/retinoic acid X receptor (RXR) heterodimer to its LPL promoter recognition element induced DNA bending at an angle of approximately 46°. Parallel studies using an optimal PPAR recognition element obtained a comparable bending angle of 56°. This is the first demonstration that binding of a PPAR protein to its recognition element causes a distortion of the DNA configuration. It indicates that PPARγ2 utilizes a common mechanism shared by other nuclear hormone receptor proteins reported to induce bending at their DNA binding sites.