TABLE 9

HNF-4γ

Receptor nomenclature NR2A3
Receptor code 4.10.1:OR:2:A3
Other names HNF4B
Molecular information Hs: 408aa, Q14541, chr. 8q211
Rn: chr. 2q24
Mm: 418aa, Q9WUU6, chr. 3 A12
DNA binding
   Structure Homodimer
   HRE core sequence AGGTCA n AGGTCA (DR-1)3,4
Partners
Agonists
Antagonists
Coactivators
Corepressors
Biologically important isoforms
Tissue distribution Endocrine, pancreas, kidney, small intestine, and testis; not found in the liver and only very weakly in the colon {Hs, Mm, Rn} [Northern blot, in situ hybridization, immunohistology]2,5
Functional assays Measurement of receptor activity using CAT and luciferase reporter genes in HeLa, HepG2, Hep3B, Saos2, Caco-2, and Hek 293 cells {Hs}1,2,4,5
Main target genes Activated: ApoA4 {Mm},4,5 ApoC3 {Mm},2 Tat {Mm},2 HNF-1α {Hs},1 AKR1C4 {Hs}6
Mutant phenotype
Human disease
  • aa, amino acids; chr., chromosome; HRE, hormone response element; CAT, chloroamphenicol acetyl transferase

  • 1. Drewes T, Senkel S, Holewa B, and Ryffel GU (1996) Human hepatocyte nuclear factor 4 isoforms are encoded by distinct and differentially expressed genes. Mol Cell Biol 16: 925-931

  • 2. Taraviras S, Mantamadiotis T, Dong-Si T, Mincheva A, Lichter P, Drewes T, Ryffel GU, Monaghan AP, and Schutz G (2000) Primary structure, chromosomal mapping, expression and transcriptional activity of murine hepatocyte nuclear factor 4gamma. Biochim Biophys Acta 1490: 21-32

  • 3. Bogan AA, Dallas-Yang Q, Ruse MD, Jr Maeda Y, Jiang G, Nepomuceno L, Scanlan TS, Cohen FE, and Sladek FM (2000) Analysis of protein dimerization and ligand binding of orphan receptor HNF4α. J Mol Biol 302: 831-851

  • 4. Archer A, Sauvaget D, Chauffeton V, Bouchet PE, Chambaz J, Pincon-Raymond M, Cardot P, Ribeiro A, and Lacasa M (2005) Intestinal apolipoprotein A-IV gene transcription is controlled by two hormone-responsive elements: a role for hepatic nuclear factor-4 isoforms. Mol Endocrinol 19: 2320-2334

  • 5. Sauvaget D, Chauffeton V, Citadelle D, Chatelet FP, Cywiner-Golenzer C, Chambaz J, Pincon-Raymond M, Cardot P, Le Beyec J, and Ribeiro A (2002) Restriction of apolipoprotein A-IV gene expression to the intestine villus depends on a hormone-responsive element and parallels differential expression of the hepatic nuclear factor 4α and γ isoforms. J Biol Chem 277: 34540-34548

  • 6. Ozeki T, Takahashi Y, Kume T, Nakayama K, Yokoi T, Nunoya K, Hara A, and Kamataki T (2001) Co-operative regulation of the transcription of human dihydrodiol dehydrogenase (DD)4/aldo-keto reductase (AKR)1C4 gene by hepatocyte nuclear factor (HNF)-4α/γ and HNF-1α. Biochem J 355: 537-544