Mouse and human retinoic acid receptor β2 promoters: Sequence comparison and localization of retinoic acid responsiveness

The retinoic acid receptor β (RARβ gene is a member of the family of retinoic acid/thyroid hormone receptor genes, encoding retinoic acid-inducible transcription factors. To study regulation of the RARβ gene, genomic clones containing the mouse and human retinoic acid receptor β2 (RARβ2) promoters were isolated and approximately 1.5 kb of upstream and downstream sequences relative to the transcriptional start site were completely sequenced. Both the mouse and human RARβ2 promoters are highly homologous around the transcription initiation site, with perfect conservation of the TATA box and retinoic acid responsive element (RARE). Promoter activation studies in P19 EC cells show, that the RARE in both the human and mouse promoters confers RA-responsiveness to the RARβ2 promoter. However, sequences located immediately upstream of the RARE also confer RA-inducibility to both the mouse and human RARβ2 gene promoters. This region contains conserved consensus sequences for a TPA-responsive element (TRE) and cAMP-responsive element (CRE), suggesting that in addition to regulation by RA receptors other transcription factors regulate RAR/β2 expression in EC cells. Furthermore, the availability of the mouse RARβ2 promoter should facilitate studies for transgene expression and gene targeting experiments in embryonic stem cells.