A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter

W. C. Smith, H. Nakshatri, P. Leroy, J. Rees, P. Chambon

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

Abstract

Genomic and cDNA sequences for the mouse cellular retinol binding protein I (mCRBPI) are presented. A specific cis-acting element responsible for retinoic acid (RA) inducibility of the mCRBPI promoter was identified and characterized. Deletion mapping of a CRBPI promoter-chloramphenicol acetyltransferase reporter gene construct localized this element to a 259 bp restriction fragment located ~1 kb upstream from the transcription start-site. A sequence closely resembling the previously characterized RA response element (RARE) of the RA receptor β2 (RAR-β2) promoter, and consisting of a direct repeat of the motif 5'-GGTCA-3' separated by three nucleotides, was found within this restriction fragment. Mutation of these 5'-GGTCA-3' motifs to GGAGC and GGGGC abolished RA-inducible transcription whereas a mutation to a direct repeat of the GTTCA motif found in the RARE of the RAR-β2 promoter resulted in enhanced inducibility. Oligonucleotides containing the direct repeat of the GGTCA motif were able to confer RA-dependent transcriptional enhancement to the herpes simplex thymidine kinase promoter, as well as to bind directly all three retinoic acid receptors (RARs) α, β and γ, as determined by gel retardation/shift assays. The control of CRBPI gene transcription by RA-RAR complexes interacting with the RARE characterized here may correspond to a feedback mechanism important in regulating retinoid metabolism and action.

Original languageEnglish (US)
Pages (from-to)2223-2230
Number of pages8
JournalEMBO Journal
Volume10
Issue number8
DOIs
StatePublished - 1991

Keywords

  • RAR
  • RARE
  • mouse CRBPI cDNA
  • retinoic acid receptors
  • transcriptional control

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter'. Together they form a unique fingerprint.

Cite this