Gene structure and functional analysis of the human Na+/phosphate co-transporter.
Three lambda phage clones encompassing the Na+/phosphate co-transporter (NaPi-3) gene and its 5' flanking region were isolated from a human genomic DNA library. The gene comprises 13 exons and 12 introns and spans approx. 14 kb. All exon-intron junctions conform to the GT/AG rule. The major transcription-initiation site was determined by primer-extension analysis and is an adenosine residue 57 bp upstream of the 3' end of the first exon. There is a typical TATA box 28 bp upstream of the major transcription-initiation site and various cis-acting elements, including a cAMP-responsive element, AP-1, AP-2 and SP-1 sites in the 5' flanking region. This region also contains three direct-repeat-like sequences that resemble the consensus binding sequence for members of the steroid-thyroid hormone receptor superfamily, including vitamin D. Deletion analysis suggests that the region from nt-2409 to nt-1259 in the 5' flanking region may be involved in kidney-specific gene expression. Vitamin D responsiveness of the NaPi-3 promoter was also detected in COS-7 cells co-transfected with a human vitamin D receptor expression vector. The presence of the three vitamin D receptor- responsive elements in the NaPi-3 promoter may be important in mediating the enhanced expression of the gene by 1,25-dihydroxyvitamin D3.
Taketani
Y
Y
Department of Clinical Nutrition, School of Medicine, University of Tokushima, Kuramoto-cho 3, Tokushima 770, Japan.
Miyamoto
K i
Ki
Tanaka
K
K
Katai
K
K
Chikamori
M
M
Tatsumi
S
S
Segawa
H
H
Yamamoto
H
H
Morita
K
K
Takeda
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002117:Calcitriol / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D012326:RNA Splicing; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014158:Transcription, Genetic; D014807:Vitamin D / Q000494:pharmacology
D002352:Carrier Proteins; D018076:DNA, Complementary; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014807:Vitamin D; D002117:Calcitriol