Home LiteratureArticle Details
PMID: 7831301 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The orphan receptors COUP-TF and HNF-4 serve as accessory factors required for induction of phosphoenolpyruvate carboxykinase gene transcription by glucocorticoids.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 2 ·1995-01-17 ·Pages 412-6

Hall RK, Sladek FM, Granner DK

Abstract

Glucocorticoids stimulate hepatic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) gene expression, thereby increasing the rate of gluconeogenesis. The effect of glucocorticoids on PEPCK gene expression is mediated by a set of promoter elements collectively referred to as the glucocorticoid response unit. The response unit spans a 100-bp segment and includes two glucocorticoid receptor binding sites (GR1 and GR2) and two accessory factor binding sites (AF1 and AF2), all of which are required for a maximal glucocorticoid response. The AF1 element also serves as a retinoic acid response element and may be involved in developmental and tissue-specific expression of the gene. In this study we report that COUP-TF and HNF-4, two orphan members of the nuclear receptor superfamily, bind to the AF1 element and function as accessory factors for the glucocorticoid response of the PEPCK gene.

MeSH Terms
Animals COUP Transcription Factor I DNA-Binding Proteins/metabolism Enzyme Induction/drug effects Gene Expression Regulation/drug effects Glucocorticoids/pharmacology Gluconeogenesis/physiology Hepatocyte Nuclear Factor 4 Liver/pathology Nuclear Proteins/metabolism Phosphoenolpyruvate Carboxykinase (GTP)/biosynthesis Phosphoproteins Promoter Regions, Genetic/genetics Protein Binding Rats Receptors, Glucocorticoid/metabolism Receptors, Interferon/metabolism Transcription Factors/metabolism Transcription, Genetic/drug effects Tumor Cells, Cultured
Chemicals
COUP Transcription Factor I DNA-Binding Proteins Glucocorticoids Hepatocyte Nuclear Factor 4 Nr2f1 protein, rat Nuclear Proteins Phosphoproteins Receptors, Glucocorticoid Receptors, Interferon Transcription Factors Phosphoenolpyruvate Carboxykinase (GTP)
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hall R K
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, TN 37232-0615.
Sladek F M
Granner D K
References (52)
52 references, click to expand
  1. Tissue-specific expression of the gene encoding hepatocyte nuclear factor 1 may involve hepatocyte nuclear factor 4.
    Genes Dev. 1991 Dec;5(12A):2225-34 PMID: 1748280
  2. Complex hormone response unit regulating transcription of the phosphoenolpyruvate carboxykinase gene: from metabolic pathways to molecular biology.
    Recent Prog Horm Res. 1991;47:319-46; discussion 346-8 PMID: 1745824
  3. Tissue-specific, developmental, hormonal, and dietary regulation of rat phosphoenolpyruvate carboxykinase-human growth hormone fusion genes in transgenic mice.
    Mol Cell Biol. 1992 Mar;12(3):1007-20 PMID: 1545785
  4. Differential regulation of the rat phosphoenolpyruvate carboxykinase gene expression in several tissues of transgenic mice.
    Mol Cell Biol. 1992 Mar;12(3):1396-403 PMID: 1545820
  5. 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):1708-18 PMID: 1312668
  6. Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis.
    Annu Rev Physiol. 1992;54:885-909 PMID: 1562196
  7. Half-site spacing and orientation determines whether thyroid hormone and retinoic acid receptors and related factors bind to DNA response elements as monomers, homodimers, or heterodimers.
    Mol Endocrinol. 1992 Mar;6(3):429-42 PMID: 1316541
  8. Metabolic control of gene expression: in vivo studies with transgenic mice.
    Trends Biochem Sci. 1992 Jan;17(1):40-4 PMID: 1585454
  9. Repression by ARP-1 sensitizes apolipoprotein AI gene responsiveness to RXR alpha and retinoic acid.
    Mol Cell Biol. 1992 Aug;12(8):3380-9 PMID: 1321332
  10. Disruption of a binding site for hepatocyte nuclear factor 4 results in hemophilia B Leyden.
    Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6300-3 PMID: 1631121
  11. Transcriptional regulation of human apolipoprotein genes ApoB, ApoCIII, and ApoAII by members of the steroid hormone receptor superfamily HNF-4, ARP-1, EAR-2, and EAR-3.
    J Biol Chem. 1992 Aug 5;267(22):15849-60 PMID: 1639815
  12. Specificity of a retinoic acid response element in the phosphoenolpyruvate carboxykinase gene promoter: consequences of both retinoic acid and thyroid hormone receptor binding.
    Mol Cell Biol. 1991 Oct;11(10):5164-70 PMID: 1656224
  13. Kainate binding to the AMPA receptor in rat brain.
    Neurochem Res. 1994 Jun;19(6):777-82 PMID: 7520541
  14. Chicken ovalbumin upstream promoter transcription factor (COUP-TF) dimers bind to different GGTCA response elements, allowing COUP-TF to repress hormonal induction of the vitamin D3, thyroid hormone, and retinoic acid receptors.
    Mol Cell Biol. 1992 Sep;12(9):4153-63 PMID: 1324415
  15. COUP orphan receptors are negative regulators of retinoic acid response pathways.
    Mol Cell Biol. 1992 Oct;12(10):4666-76 PMID: 1328857
  16. Elements responsible for hormonal control and tissue specificity of L-type pyruvate kinase gene expression in transgenic mice.
    Mol Cell Biol. 1992 Nov;12(11):4852-61 PMID: 1406667
  17. Activation of the phosphoenolpyruvate carboxykinase gene retinoic acid response element is dependent on a retinoic acid receptor/coregulator complex.
    Mol Cell Biol. 1992 Dec;12(12):5527-35 PMID: 1333043
  18. Multiple mechanisms of chicken ovalbumin upstream promoter transcription factor-dependent repression of transactivation by the vitamin D, thyroid hormone, and retinoic acid receptors.
    J Biol Chem. 1993 Feb 25;268(6):4152-60 PMID: 8382695
  19. COUP-TF acts as a competitive repressor for estrogen receptor-mediated activation of the mouse lactoferrin gene.
    Mol Cell Biol. 1993 Mar;13(3):1836-46 PMID: 8441416
  20. Glucocorticoid receptor-cAMP response element-binding protein interaction and the response of the phosphoenolpyruvate carboxykinase gene to glucocorticoids.
    J Biol Chem. 1993 Mar 15;268(8):5353-6 PMID: 8449898
  21. HNF-4 increases activity of the rat Apo A1 gene.
    Nucleic Acids Res. 1993 Mar 11;21(5):1205-11 PMID: 8464705
  22. Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) represses transcription from the promoter of the gene for ornithine transcarbamylase in a manner antagonistic to hepatocyte nuclear factor-4 (HNF-4).
    J Biol Chem. 1993 May 25;268(15):11125-33 PMID: 8496174
  23. Functional interaction of nuclear factors EF-C, HNF-4, and RXR alpha with hepatitis B virus enhancer I.
    J Virol. 1993 Jul;67(7):3940-50 PMID: 8389913
  24. Activation of the tyrosine aminotransferase gene is dependent on synergy between liver-specific and hormone-responsive elements.
    Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5479-83 PMID: 8100067
  25. Transferrin gene as a model for liver-specific gene expression.
    Biol Cell. 1993;77(1):63-5 PMID: 8518746
  26. Hepatocyte nuclear factor-4 activates medium chain acyl-CoA dehydrogenase gene transcription by interacting with a complex regulatory element.
    J Biol Chem. 1993 Jul 5;268(19):13805-10 PMID: 8314750
  27. Orphan receptor HNF-4 and bZip protein C/EBP alpha bind to overlapping regions of the apolipoprotein B gene promoter and synergistically activate transcription.
    J Biol Chem. 1993 Aug 5;268(22):16831-8 PMID: 8344962
  28. Chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds to a peroxisome proliferator-responsive element and antagonizes peroxisome proliferator-mediated signaling.
    J Biol Chem. 1993 Sep 15;268(26):19169-72 PMID: 8396126
  29. Analysis of the rat hepatocyte nuclear factor (HNF) 1 gene promoter: synergistic activation by HNF4 and HNF1 proteins.
    Nucleic Acids Res. 1993 Aug 11;21(16):3731-6 PMID: 8367288
  30. Factors participating in the liver-specific expression of the human apolipoprotein A-II gene and their significance for transcription.
    Biochemistry. 1993 Sep 7;32(35):9080-93 PMID: 8369280
  31. The patterns of binding of RAR, RXR and TR homo- and heterodimers to direct repeats are dictated by the binding specificites of the DNA binding domains.
    EMBO J. 1993 Dec 15;12(13):5029-41 PMID: 8262045
  32. Determination of tissue specificity of the enhancer by combinatorial operation of tissue-enriched transcription factors. Both HNF-4 and C/EBP beta are required for liver-specific activity of the ornithine transcarbamylase enhancer.
    J Biol Chem. 1994 Jan 14;269(2):1323-31 PMID: 8288597
  33. The directly repeated RG(G/T)TCA motifs of the rat and mouse cellular retinol-binding protein II genes are promiscuous binding sites for RAR, RXR, HNF-4, and ARP-1 homo- and heterodimers.
    J Biol Chem. 1994 Jan 14;269(2):890-902 PMID: 8288643
  34. Characterization of a negative retinoic acid response element in the murine Oct4 promoter.
    Mol Cell Biol. 1994 Feb;14(2):1122-36 PMID: 8289793
  35. Transcriptional control of metabolic regulation genes by carbohydrates.
    FASEB J. 1994 Jan;8(1):28-35 PMID: 8299888
  36. cAMP stimulates transcription of the gene for cytosolic phosphoenolpyruvate carboxykinase in rat liver nuclei.
    Proc Natl Acad Sci U S A. 1982 Sep;79(17):5137-41 PMID: 6291025
  37. Inhibition of transcription of the phosphoenolpyruvate carboxykinase gene by insulin.
    Nature. 1983 Oct 6-12;305(5934):549-51 PMID: 6353247
  38. Tissue-specific in vitro transcription from the mouse albumin promoter.
    Cell. 1986 Dec 5;47(5):767-76 PMID: 3779841
  39. The effect of phorbol esters and diacylglycerol on expression of the phosphoenolpyruvate carboxykinase (GTP) gene in rat hepatoma H4IIE cells.
    J Biol Chem. 1986 Dec 25;261(36):16848-53 PMID: 3023368
  40. Identification of two factors required for transcription of the ovalbumin gene.
    Mol Cell Biol. 1986 Dec;6(12):4259-67 PMID: 3796602
  41. A rapid, sensitive, and inexpensive assay for chloramphenicol acetyltransferase.
    DNA. 1987 Apr;6(2):173-8 PMID: 3472867
  42. Location and characterization of two widely separated glucocorticoid response elements in the phosphoenolpyruvate carboxykinase gene.
    Mol Cell Biol. 1988 Jan;8(1):96-104 PMID: 3422101
  43. A regulatory element in the ApoCIII promoter that directs hepatic specific transcription binds to proteins in expressing and nonexpressing cell types.
    J Biol Chem. 1989 Sep 25;264(27):16132-7 PMID: 2777781
  44. The genes of hepatic glucose metabolism.
    J Biol Chem. 1990 Jun 25;265(18):10173-6 PMID: 2191945
  45. Characterization of a complex glucocorticoid response unit in the phosphoenolpyruvate carboxykinase gene.
    Mol Cell Biol. 1990 Sep;10(9):4712-9 PMID: 2388623
  46. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily.
    Science. 1991 Feb 1;251(4993):561-5 PMID: 1899293
  47. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily.
    Genes Dev. 1990 Dec;4(12B):2353-65 PMID: 2279702
  48. A retinoic acid response element is part of a pleiotropic domain in the phosphoenolpyruvate carboxykinase gene.
    Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2184-8 PMID: 1848696
  49. The different tissue transcription patterns of genes for HNF-1, C/EBP, HNF-3, and HNF-4, protein factors that govern liver-specific transcription.
    Proc Natl Acad Sci U S A. 1991 May 1;88(9):3807-11 PMID: 2023930
  50. Orphan receptor HNF-4 and liver-specific gene expression.
    Receptor. 1993 Fall;3(3):223-32 PMID: 8167573
  51. Integration of multiple signals through a complex hormone response unit in the phosphoenolpyruvate carboxykinase gene promoter.
    Mol Endocrinol. 1994 May;8(5):585-94 PMID: 8058068
  52. A transcriptional hierarchy involved in mammalian cell-type specification.
    Nature. 1992 Jan 30;355(6359):457-61 PMID: 1734282
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.2.412
Published
1995-01-17
Pages
412-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC42750
Subset
IM
Grants
NIDDK NIH HHS · DK20593 · United States
NIDDK NIH HHS · DK35107 · United States
External Links
PubMed source DOI: 10.1073/pnas.92.2.412 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2