IDENTIFICATION OF A NOVEL VITAMIN-D RESPONSE ELEMENT FROM THE RAT GENOME

1 alpha,25-Dihydroxyvitamin D-3 [1,25-(OH)(2)D-3], the active form of vitamin D-3, has been thought to be a multifunctional agent. In order to discover novel roles of 1,25-(OH)(2)D-3, we have been looking for n ew genes that are regulated by 1,25-(OH)(2)D-3. Because the actions of 1,25(OH)(2)D-3 are mediated through the vitamin D receptor (VDR), tha t is a DNA binding transcription factor, vitamin D regulated genes sho uld have VDR binding sites in their regulatory regions. In this paper, we describe a novel vitamin D response element (VDRE)-containing sequ ence, clone 3, which was isolated through binding to VDR. DNA sequence analysis of clone 3 did not reveal any significant similarity with se quences reported previously. Clone 3 had two regions consisting of a d irect repeated sequence of AGTTCA motifs, both of which bound to VDR i ndependently. Whereas each direct repeat sequence alone could not medi ate transcriptional activation efficiently, with their co-existence th ere was a strong response to 1,25-(OH)(2)D-3, indicating that these tw o direct repeated sequences act cooperatively.