Functional interactions of peroxisome proliferator-activated receptor, retinoid-X receptor, and Sp1 in the transcriptional regulation of the acyl-coenzyme-A oxidase promoter

Mol Endocrinol. 1995 Feb;9(2):219-31. doi: 10.1210/mend.9.2.7776972.


Peroxisome proliferator-activated receptor (PPARs) are members of the nuclear receptor superfamily. For transcriptional activation of their target genes, PPARs heterodimerize with the retinoid-X receptor (RXR). The convergence of the PPAR and RXR signaling pathways has been shown to have an important function in lipid metabolism. The promoter of the gene encoding the acyl-coenzyme-A oxidase (ACO), the rate-limiting enzyme in peroxisomal beta-oxidation of fatty acids, is a target site of PPAR action. In this study, we examined the role and the contribution of both cis-and trans-acting factors in the transcriptional regulation of this gene using transient transfections in insect cells. We identified several functional cis-acting elements present in the promoter of the ACO gene and established that PPAR-dependent as well as PPAR-independent mechanisms can activate the ACO promoter in these cells. We show that the PPAR/RXR heterodimer exerts its effect through two response elements within the ACO promoter, in synergy with the transcription factor Sp1 via five Sp1-binding sites. Furthermore, this functional interaction also occurs when Sp1 is co-expressed with PPAR or RXR alone, indicating that activation can occur independently of PPAR/RXR heterodimers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl-CoA Oxidase
  • Animals
  • Base Sequence
  • Cell Line
  • Consensus Sequence
  • Drosophila
  • Gene Expression Regulation, Enzymologic*
  • Genes, Reporter
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oxidoreductases / genetics*
  • Oxidoreductases / metabolism
  • Precipitin Tests
  • Promoter Regions, Genetic
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Retinoic Acid / metabolism*
  • Regulatory Sequences, Nucleic Acid
  • Retinoid X Receptors
  • Sp1 Transcription Factor / metabolism*
  • Transcription Factors / metabolism*
  • Transfection


  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Sp1 Transcription Factor
  • Transcription Factors
  • Oxidoreductases
  • Acyl-CoA Oxidase