DNA bending is induced by binding of the peroxisome proliferator-activated receptor gamma 2 heterodimer to its response element in the murine lipoprotein lipase promoter.
The peroxisome proliferator activated receptor gamma 2 (PPAR gamma 2) is a critical transcriptional regulator of adipogenesis. Lipoprotein lipase is one of the earliest genes induced following exposure of pre-adipocytes to PPAR gamma 2 ligands such as the thiazolidinediones. A unique PPAR gamma 2 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 PPAR gamma 2/retinoic acid X receptor (RXR) heterodimer to its LPL promoter recognition element induced DNA bending at an angle of approximately 46 degrees. Parallel studies using an optimal PPAR recognition element obtained a comparable bending angle of 56 degrees. 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 PPAR gamma 2 utilizes a common mechanism shared by other nuclear hormone receptor proteins reported to induce bending at their DNA binding sites.
Robinson
C E
CE
Zoology Department, University of Oklahoma, Norman 73019, USA.
Wu
X
X
Morris
D C
DC
Gimble
J M
JM
D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004252:DNA Mutational Analysis; D019281:Dimerization; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D008071:Lipoprotein Lipase / Q000235:genetics*; D051379:Mice; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA; D008071:Lipoprotein Lipase