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.

Abstract

We show here that the element which was previously characterized as a retinoid X receptor (RXR)-specific response element (RXRE) in the rat cellular retinol-binding protein II (CRBPII) gene is not conserved in the mouse gene. However, two conserved cis-acting elements (RE2 and RE3) located in the promoter region of the mouse and rat CRBPII genes mediate transactivation by retinoic acid receptors (RARs) and RXRs in transfected Cos-1, CV-1, and HeLa cells. The element RE3 which is the major retinoic acid (RA) response element also binds the transcription factors HNF-4 and ARP-1. HNF-4 constitutively activates the mouse CRBPII promoter, whereas ARP-1 represses the activation mediated by RARs, RXRs, and HNF-4. In contrast, RA has no effect on the activity of the mouse CRBPII promoter in the human colon carcinoma cell line CaCo-2 which constitutively expresses RAR alpha, RAR gamma, RXR alpha, HNF-4, and ARP-1, under conditions where the activity of the RAR beta 2 gene promoter is readily induced by RA. Our results suggest that the CRBPII gene may not be RA-inducible in tissues expressing HNF-4 and ARP-1, and that the RA inducibility of the CRBPII gene promoter observed in transfection experiments reflects the promiscuous binding of RARs/RXRs to HNF-4 and ARP-1 response elements.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • COUP Transcription Factor II
  • COUP Transcription Factors
  • DNA Primers / chemistry
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation*
  • Hepatocyte Nuclear Factor 4
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphoproteins*
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Retinoic Acid / metabolism*
  • Receptors, Steroid*
  • Retinoid X Receptors
  • Retinol-Binding Proteins / genetics*
  • Retinol-Binding Proteins, Cellular
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • Structure-Activity Relationship
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • COUP Transcription Factor II
  • COUP Transcription Factors
  • DNA Primers
  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 4
  • Nr2f2 protein, mouse
  • Nr2f2 protein, rat
  • Phosphoproteins
  • RBP2 protein, human
  • RNA, Messenger
  • Rbp2 protein, mouse
  • Rbp2 protein, rat
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Receptors, Steroid
  • Retinoid X Receptors
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Cellular
  • Tcfl4 protein, mouse
  • Transcription Factors

Associated data

  • GENBANK/X74153
  • GENBANK/X74154