Functional interactions between nuclear receptors recognizing a common sequence element, the direct repeat motif spaced by one nucleotide (DR-1)

J Biochem. 1998 Jun;123(6):1174-9. doi: 10.1093/oxfordjournals.jbchem.a022058.

Abstract

Direct repeat motifs composed of two hexamer half-sites spaced by a single nucleotide (DR-1) are recognized by several members of the nuclear hormone receptor superfamily. We examined, by means of gene transfection assays, the interplay between the DR-1-binding nuclear receptors commonly expressed in liver, peroxisome proliferator-activated receptor alpha (PPARalpha), hepatocyte nuclear factor-4 (HNF-4), and chicken ovalbumin upstream transcription factor I (COUP-TFI). Both PPARalpha and HNF-4 efficiently bound to the acyl-CoA oxidase gene enhancer element, but PPARalpha exhibited much stronger transactivation than HNF-4. As a result, HNF-4 suppressed the gene-activating function of PPARalpha, when they were expressed together, due to competition for a common binding site. On the other hand, HNF-4, but not PPARalpha, effectively bound to the apolipoprotein CIII gene element, and activated gene transcription. PPARalpha had no effect even when co-expressed with HNF-4. COUP-TFI bound to both elements, and suppressed the gene activation by PPARalpha and HNF-4. Thus, these nuclear receptors have individual functions in gene regulation, and exhibit complex compound effects when they co-exist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • COUP Transcription Factor I
  • Cell Line
  • Chickens
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Hepatocyte Nuclear Factor 4
  • Liver / metabolism
  • Nucleotides*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Rats
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Repetitive Sequences, Nucleic Acid
  • Sequence Analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transfection

Substances

  • COUP Transcription Factor I
  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 4
  • Nr2f1 protein, rat
  • Nucleotides
  • Phosphoproteins
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors