Nucleic Acids Research, Vol 24, Issue 15 2930-2935, Copyright © 1996 by Oxford University Press
DG Taylor, S Haubenwallner and T Leff
The HNF-4 orphan receptor is a member of the nuclear receptor family of
transcription factors and a major regulator of genes involved in
carbohydrate and lipid metabolism. As an initial step in characterizing the
role of HNF-4 in the regulation of metabolism, we have generated a dominant
negative form of HNF-4 (DN-HNF-4) that contains a defective DNA-binding
domain. In gel mobility shift assays, DN-HNF-4 did not bind an
oligonucleotide probe representing an essential HNF-4 binding site, C3P
contained in the human apo CIII promoter, but did prevent the binding of
two recombinant isoforms, HNF-4alpha1 and HNF-4alpha2, as well as
naturally-occurring HNF-4. DN-HNF-4 had no effect on the binding of
PPARgamma-RXRalpha heterodimers to a PPAR response element. In transfected
HepG2 cells, DN-HNF-4 dramatically reduced constitutive transcriptional
activity of the human apo CIII promoter and abolished the positive
transcriptional activity caused by plasmids expressing either isoform of
HNF-4. These results indicate that DN-HNF-4 is a selective dominant
negative mutant which forms defective heterodimers with wild-type HNF-4,
thereby preventing DNA binding and subsequent transcriptional activation by
HNF-4.
ARTICLES
Characterization of a dominant negative mutant form of the HNF-4 orphan receptor
Department of Biotechnology, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Hirota, J.-i. Sakamaki, J. Ishida, Y. Shimamoto, S. Nishihara, N. Kodama, K. Ohta, M. Yamamoto, K. Tanimoto, and A. Fukamizu A Combination of HNF-4 and Foxo1 Is Required for Reciprocal Transcriptional Regulation of Glucokinase and Glucose-6-phosphatase Genes in Response to Fasting and Feeding J. Biol. Chem., November 21, 2008; 283(47): 32432 - 32441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Perilhou, C. Tourrel-Cuzin, P. Zhang, I. Kharroubi, H. Wang, V. Fauveau, D. K. Scott, C. B. Wollheim, and M. Vasseur-Cognet The MODY1 Gene for Hepatocyte Nuclear Factor 4{alpha} and a Feedback Loop Control COUP-TFII Expression in Pancreatic Beta Cells Mol. Cell. Biol., July 15, 2008; 28(14): 4588 - 4597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Jahan and J. Y. L. Chiang Cytokine regulation of human sterol 12{alpha}-hydroxylase (CYP8B1) gene Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G685 - G695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Gautier-Stein, G. Mithieux, and F. Rajas A Distal Region Involving Hepatocyte Nuclear Factor 4{alpha} and CAAT/Enhancer Binding Protein Markedly Potentiates the Protein Kinase A Stimulation of the Glucose-6-Phosphatase Promoter Mol. Endocrinol., January 1, 2005; 19(1): 163 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Massillon, I. J. Arinze, C. Xu, and F. Bone Regulation of Glucose-6-phosphatase Gene Expression in Cultured Hepatocytes and H4IIE Cells by Short-chain Fatty Acids: ROLE OF HEPATIC NUCLEAR FACTOR-4{alpha} J. Biol. Chem., October 17, 2003; 278(42): 40694 - 40701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-F. Louet, G. Hayhurst, F. J. Gonzalez, J. Girard, and J.-F. Decaux The Coactivator PGC-1 Is Involved in the Regulation of the Liver Carnitine Palmitoyltransferase I Gene Expression by cAMP in Combination with HNF4alpha and cAMP-response Element-binding Protein (CREB) J. Biol. Chem., October 4, 2002; 277(41): 37991 - 38000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Chen, E. Owsley, Y. Yang, D. Stroup, and J. Y. L. Chiang Nuclear receptor-mediated repression of human cholesterol 7{alpha}-hydroxylase gene transcription by bile acids J. Lipid Res., September 1, 2001; 42(9): 1402 - 1412. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Makita, G. Hernandez-Hoyos, T. H.-P. Chen, H. Wu, E. V. Rothenberg, and H. M. Sucov A developmental transition in definitive erythropoiesis: erythropoietin expression is sequentially regulated by retinoic acid receptors and HNF4 Genes & Dev., April 1, 2001; 15(7): 889 - 901. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Lausen, H. Thomas, I. Lemm, M. Bulman, M. Borgschulze, A. Lingott, A. T. Hattersley, and G. U. Ryffel Naturally occurring mutations in the human HNF4{alpha} gene impair the function of the transcription factor to a varying degree Nucleic Acids Res., January 15, 2000; 28(2): 430 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Reddy, W. Yang, D. G. Taylor, X.-q. Shen, D. Oxender, G. Kust, and T. Leff Mitogen-activated Protein Kinase Regulates Transcription of the ApoCIII Gene. INVOLVEMENT OF THE ORPHAN NUCLEAR RECEPTOR HNF4 J. Biol. Chem., November 12, 1999; 274(46): 33050 - 33056. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Z. Kapitskaya, N. T. Dittmer, K. W. Deitsch, W.-L. Cho, D. G. Taylor, T. Leff, and A. S. Raikhel Three Isoforms of a Hepatocyte Nuclear Factor-4 Transcription Factor with Tissue- and Stage-specific Expression in the Adult Mosquito J. Biol. Chem., November 6, 1998; 273(45): 29801 - 29810. [Abstract] [Full Text] [PDF]
|
|