Skip to main content

Transcriptional regulation of the cholesteryl ester transfer protein gene by the orphan nuclear hormone receptor apolipoprotein AI regulatory protein-1.

Publication ,  Journal Article
Gaudet, F; Ginsburg, GS
Published in: J Biol Chem
December 15, 1995

We have defined a 105-base pair tissue-restricted promoter for the cholesteryl ester transfer protein (CETP) gene that contains a nuclear hormone receptor response element essential for transcriptional activity. DNaseI protection and electrophoretic mobility shift assays showed specific binding of nuclear extracts from HepG2 (hepatic) and Caco-2 (intestinal) cells (expressing cell types) to 3 sites (designated A (-26 to -57), B (-59 to -87), and C (-93 to -118)) within the 105-base pair minimal promoter element between -138 and -33. Mutagenesis studies indicated that the function of the promoter was dependent upon synergistic interactions between transcription factors bound to these sites. Mutation of site C reduced transcription by 50 and 80%, respectively, in HepG2 and Caco-2 cells, and electrophoretic mobility shift assays showed that nuclear hormone receptors, including ARP-1 and its homologue Ear-3/COUP-TF, were occupants of site C in both of these cell types. Overexpression of ARP-1 or Ear-3/COUP-TF with CETP promoter/chloramphenicol acetyltransferase gene reporter plasmids repressed transcriptional activity of the CETP promoter containing sequences up to -300, but activated transcription in the context of larger constructs containing sequences up to -636. Thus ARP-1 may assume a dichotomous role as both a transcriptional repressor and a transcriptional activator dependent on the promoter context. In addition, the architecture of the CETP gene promoter suggests that its expression is under the control of multiple transcriptional signaling pathways mediated by inducible transcription factors as well as nuclear hormone receptors.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 15, 1995

Volume

270

Issue

50

Start / End Page

29916 / 29922

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Recombinant Proteins
  • Receptors, Steroid
  • Polymerase Chain Reaction
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gaudet, F., & Ginsburg, G. S. (1995). Transcriptional regulation of the cholesteryl ester transfer protein gene by the orphan nuclear hormone receptor apolipoprotein AI regulatory protein-1. J Biol Chem, 270(50), 29916–29922. https://doi.org/10.1074/jbc.270.50.29916
Gaudet, F., and G. S. Ginsburg. “Transcriptional regulation of the cholesteryl ester transfer protein gene by the orphan nuclear hormone receptor apolipoprotein AI regulatory protein-1.J Biol Chem 270, no. 50 (December 15, 1995): 29916–22. https://doi.org/10.1074/jbc.270.50.29916.
Gaudet, F., and G. S. Ginsburg. “Transcriptional regulation of the cholesteryl ester transfer protein gene by the orphan nuclear hormone receptor apolipoprotein AI regulatory protein-1.J Biol Chem, vol. 270, no. 50, Dec. 1995, pp. 29916–22. Pubmed, doi:10.1074/jbc.270.50.29916.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 15, 1995

Volume

270

Issue

50

Start / End Page

29916 / 29922

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Recombinant Proteins
  • Receptors, Steroid
  • Polymerase Chain Reaction
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Mice