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

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.