An intact DNA-binding domain is not required for peroxisome proliferator-activated receptor gamma (PPARgamma) binding and activation on some PPAR response elements

J Biol Chem. 2005 Feb 4;280(5):3529-40. doi: 10.1074/jbc.M411422200. Epub 2004 Nov 29.


Peroxisome proliferator-activated receptor gamma (PPARgamma) interacts with retinoid X receptor (RXR) on PPAR response elements (PPREs) to regulate transcription of PPAR-responsive genes. To investigate the binding of PPARgamma and RXR to PPREs, three mutations were constructed in the DNA-binding domains of PPARgamma; two of the mutants maintained the structure of zinc finger I (PPARgamma-GS and PPARgamma-AA), and a third mutation disrupted the protein structure of zinc finger I (PPARgamma-CS). Results indicated that the mutations of PPARgamma that maintained intact zinc fingers were capable of binding to a variety of PPREs in the presence of RXR and could activate transcription on several PPREs. In parallel, a mutation was created in the DNA-binding domain of RXRalpha that maintained the structure of the zinc fingers (RXR-GS) but did not bind DNA and was transcriptionally inactive. Examination of the 3' half-site of several PPREs revealed that variations from the consensus sequence reduced or abolished transcriptional activity, but conversion to consensus improved transcriptional activity with PPARgamma-GS and PPARgamma-AA. Examination of the 5' half-site indicated that the upstream three nucleotides were more important for transcriptional activity than the downstream three nucleotides. Our data demonstrated that stringent binding of RXR to the 3' half-site of a PPRE is more influential on the binding of the PPARgamma/RXR heterodimer than the ability of PPARgamma to bind DNA. Thus, unlike RXR, PPARgamma exhibits promiscuity in binding on a PPRE, suggesting that the definition of a PPRE for PPARgamma may need to be expanded.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyl-CoA Oxidase / genetics
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Consensus Sequence
  • Dimerization
  • Mice
  • Molecular Sequence Data
  • Mutagenesis
  • PPAR gamma / chemistry
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism*
  • Phosphoenolpyruvate Carboxykinase (GTP) / genetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Response Elements / physiology*
  • Retinoid X Receptors / metabolism
  • Transcriptional Activation / physiology*
  • Transfection


  • PPAR gamma
  • Retinoid X Receptors
  • Acyl-CoA Oxidase
  • Phosphoenolpyruvate Carboxykinase (GTP)