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Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells.

Publication ,  Journal Article
Mietus-Snyder, M; Sladek, FM; Ginsburg, GS; Kuo, CF; Ladias, JA; Darnell, JE; Karathanasis, SK
Published in: Mol Cell Biol
April 1992

Apolipoprotein CIII (apoCIII), a lipid-binding protein involved in the transport of triglycerides and cholesterol in the plasma, is synthesized primarily in the liver and the intestine. A cis-acting regulatory element, C3P, located at -90 to -66 upstream from the apoCIII gene transcriptional start site (+1), is necessary for maximal expression of the apoCIII gene in human hepatoma (HepG2) and intestinal carcinoma (Caco2) cells. This report shows that three members of the steroid receptor superfamily of transcription factors, hepatocyte nuclear factor 4 (HNF-4), apolipoprotein AI regulatory protein 1 (ARP-1), and Ear3/COUP-TF, act at the C3P site. HNF-4 activates apoCIII gene expression in HepG2 and Caco2 cells, while ARP-1 and Ear3/COUP-TF repress its expression in the same cells. HNF-4 activation is abolished by increasing amounts of ARP-1 or Ear3/COUP-TF, and repression by ARP-1 or Ear3/COUP-TF is alleviated by increasing amounts of HNF-4. HNF-4 and ARP-1 bind with similar affinities to the C3P site, suggesting that their opposing transcriptional effects may be mediated by direct competition for DNA binding. HNF-4 and ARP-1 mRNAs are present within the same cells in the liver and intestine, and protein extracts from hepatic tissue, HepG2, and Caco2 cells contain significantly more HNF-4 than ARP-1 or Ear3/COUP-TF binding activities. These findings suggest that the transcription of the apoCIII gene in vivo is dependent, at least in part, upon the intracellular balance of these positive and negative regulatory factors.

Duke Scholars

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

April 1992

Volume

12

Issue

4

Start / End Page

1708 / 1718

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Transcription Factors
  • Tissue Distribution
  • Recombinant Fusion Proteins
  • Receptors, Steroid
  • Promoter Regions, Genetic
  • Phosphoproteins
  • Molecular Sequence Data
  • Liver Neoplasms
 

Citation

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Mietus-Snyder, M., Sladek, F. M., Ginsburg, G. S., Kuo, C. F., Ladias, J. A., Darnell, J. E., & Karathanasis, S. K. (1992). Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mol Cell Biol, 12(4), 1708–1718. https://doi.org/10.1128/mcb.12.4.1708-1718.1992
Mietus-Snyder, M., F. M. Sladek, G. S. Ginsburg, C. F. Kuo, J. A. Ladias, J. E. Darnell, and S. K. Karathanasis. “Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells.Mol Cell Biol 12, no. 4 (April 1992): 1708–18. https://doi.org/10.1128/mcb.12.4.1708-1718.1992.
Mietus-Snyder, M., et al. “Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells.Mol Cell Biol, vol. 12, no. 4, Apr. 1992, pp. 1708–18. Pubmed, doi:10.1128/mcb.12.4.1708-1718.1992.
Mietus-Snyder M, Sladek FM, Ginsburg GS, Kuo CF, Ladias JA, Darnell JE, Karathanasis SK. Antagonism between apolipoprotein AI regulatory protein 1, Ear3/COUP-TF, and hepatocyte nuclear factor 4 modulates apolipoprotein CIII gene expression in liver and intestinal cells. Mol Cell Biol. 1992 Apr;12(4):1708–1718.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

April 1992

Volume

12

Issue

4

Start / End Page

1708 / 1718

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Transcription Factors
  • Tissue Distribution
  • Recombinant Fusion Proteins
  • Receptors, Steroid
  • Promoter Regions, Genetic
  • Phosphoproteins
  • Molecular Sequence Data
  • Liver Neoplasms