PUBLICATION

Retinoid X receptor (RXR) within the RXR-retinoic acid receptor heterodimer binds its ligand and enhances retinoid-dependent gene expression

Authors
Minucci, S., Leid, M., Toyama, R., Saint-Jeannet, J.P., Peterson, V.J., Horn, V., Ishmael, J.E., Bhattacharyya, N., Dey, A., Dawid, I.B., and Ozato, K.
ID
ZDB-PUB-970324-5
Date
1997
Source
Molecular and cellular biology   17(2): 644-655 (Journal)
Registered Authors
Dawid, Igor B., Ozato, Kenjiro, Toyama, Reiko
Keywords
none
MeSH Terms
  • Animals
  • Blastocyst
  • DNA/metabolism
  • Embryo, Nonmammalian/drug effects
  • Embryonal Carcinoma Stem Cells
  • Gene Expression Regulation/drug effects*
  • Humans
  • Ligands
  • Mice
  • Neoplastic Stem Cells
  • Peptide Fragments
  • Promoter Regions, Genetic/genetics
  • Protein Conformation/drug effects
  • Receptors, Retinoic Acid/chemistry
  • Receptors, Retinoic Acid/genetics
  • Receptors, Retinoic Acid/metabolism*
  • Recombinant Fusion Proteins
  • Retinoid X Receptors
  • Retinoids/pharmacology*
  • Teratogens/pharmacology
  • Transcription Factors/chemistry
  • Transcription Factors/metabolism*
  • Transcriptional Activation
  • Xenopus/embryology
  • Zebrafish/embryology
PubMed
9001218 Full text @ Mol. Cell. Biol.
Abstract
Retinoic acid receptor (RAR) and retinoid X receptor (RXR) form heterodimers and regulate retinoid-mediated gene expression. We studied binding of RXR- and RAR-selective ligands to the RXR-RAR heterodimer and subsequent transcription. In limited proteolysis analyses, both RXR and RAR in the heterodimer bound their respective ligands and underwent a conformational change in the presence of a retinoic acid-responsive element. In reporter analyses, the RAR ligand (but not the RXR ligand), when added singly, activated transcription, but coaddition of the two ligands led to synergistic activation of transcription. This activation required the AF-2 domain of both RXR and RAR. Genomic footprinting analysis was performed with P19 embryonal carcinoma cells, in which transcription of the RARbeta gene is induced upon retinoid addition. Paralleling the reporter activation data, only the RAR ligand induced in vivo occupancy of the RARbeta2 promoter when added singly. However, at suboptimal concentrations of RAR ligand, coaddition of the RXR liganded RXR and RAR both participate in transcription. Finally, when these ligands were tested for teratogenic effects on zebra fish and Xenopus embryos, we found that coadministration of the RXR and RAR ligands caused more severe abnormalities in these embryos than either ligand alone, providing biological support for the synergistic action of the two ligands.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping