Identification of a novel vitamin D response element from the rat genome.
1 alpha,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the active form of vitamin D3, has been thought to be a multifunctional agent. In order to discover novel roles of 1,25-(OH)2D3, we have been looking for new genes that are regulated by 1,25-(OH)2D3. Because the actions of 1,25-(OH)2D3 are mediated through the vitamin D receptor (VDR), that is a DNA binding transcription factor, vitamin D regulated genes should have VDR binding sites in their regulatory regions. In this paper, we describe a novel vitamin D response element (VDRE)-containing sequence, clone 3, which was isolated through binding to VDR. DNA sequence analysis of clone 3 did not reveal any significant similarity with sequences reported previously. Clone 3 had two regions consisting of a direct repeated sequence of AGTTCA motifs, both of which bound to VDR independently. Whereas each direct repeat sequence alone could not mediate transcriptional activation efficiently, with their co-existence there was a strong response to 1,25-(OH)2D3, indicating that these two direct repeated sequences act cooperatively.
Sakoda
K
K
Department of Environmental Biochemistry, Faculty of Pharmaceutical Sciences, Osaka University.
Suzuki
A
A
Arai
S
S
Imagawa
M
M
Nishikawa
J
J
Nishihara
T
T
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002117:Calcitriol / Q000494:pharmacology; D003001:Cloning, Molecular; D004247:DNA / Q000187:drug effects / Q000378:metabolism*; D016678:Genome; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014807:Vitamin D / Q000378:metabolism* / Q000494:pharmacology
D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014807:Vitamin D; D004247:DNA; D002117:Calcitriol