A retinoic acid response element from the rat CRBPI promoter is activated by an RAR/RXR heterodimer

The expression of the rat cellular retinol binding protein I (rCRBPI) can be upregulated in vivo by retinoic acid (RA). Here we have analyzed the rCRBPI promoter region and compared it to the corresponding mouse sequence. We find that the CRBPI 5' flanking region has been highly conserved between rat and mouse, including a RA response element (RARE) approximately 1 kb upstream of the start of transcription. The RARE is of the direct repeat type with a two nucleotide spacer. Like other direct repeat RAREs, this response element is activated by RAR alpha and beta but not by RAR gamma 1. Furthermore, the rCRBPI-RARE is most effectively activated when both RAR and RXR are present. In addition RAR/RXR heterodimers are required for efficient binding to the rCRBPI-RARE, while RARs or RXR alone do not interact effectively with this response element. The rCRBPI gene is therefore most likely activated in vitro by a RAR/RXR heterodimer.