Evidence for two distinct retinoic acid response pathways for HOXB1 gene regulation.

We have recently identified a promoter proximal retinoic acid (RA)-responsive site in the 5' region of the HOXB1 gene. In this report, we have identified the second RA-responsive site in the 3' region of the HOXB1 gene. This site also consists of a DR-2-type target of RA receptor.retinoid X receptor complex (DR-2B) and the binding site for a distinct RA-dependent coactivator termed retinoid-activating protein, which shows a different tissue-specific spectrum from the 5' responsive site. This indicates that the activation of the HOXB1 gene is achieved through two distinct pathways. These data define an unusual regulatory mechanism leading to the establishment of HOXB1 gene expression.