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

William C. Smith, Harikrishna Nakshatri, Pierre Leroy, Jonathan Rees, Pierre Chambon

Research output: Contribution to journalArticle

181 Citations (Scopus)

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
StatePublished - 1991
Externally publishedYes

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Cellular Retinol-Binding Proteins
Response Elements
Tretinoin
Retinoic Acid Receptors
Nucleic Acid Repetitive Sequences
Transcription
Genes
Mutation
Herpes Simplex
Chloramphenicol O-Acetyltransferase
Thymidine Kinase
Transcription Initiation Site
Retinoids
Electrophoretic Mobility Shift Assay
Reporter Genes
Metabolism
Oligonucleotides
Assays
Nucleotides
Complementary DNA

Keywords

  • Mouse CRBPI cDNA
  • RAR
  • RARE
  • Retinoic acid receptors
  • Transcriptional control

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter. / Smith, William C.; Nakshatri, Harikrishna; Leroy, Pierre; Rees, Jonathan; Chambon, Pierre.

In: EMBO Journal, Vol. 10, No. 8, 1991, p. 2223-2230.

Research output: Contribution to journalArticle

Smith, William C. ; Nakshatri, Harikrishna ; Leroy, Pierre ; Rees, Jonathan ; Chambon, Pierre. / A retinoic acid response element is present in the mouse cellular retinol binding protein I (mCRBPI) promoter. In: EMBO Journal. 1991 ; Vol. 10, No. 8. pp. 2223-2230.
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AB - 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.

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