Parathyroid Hormone Activation of the 25-hydroxyvitamin D3-1α -hydroxylase Gene Promoter

The DNA flanking the 5′sequence of the mouse 1α -hydroxylase gene has been cloned and sequenced. A TATA box has been located at -30 bp and aCCAAT box has been located at -79 bp. The gene's promoter activity has been demonstrated by using a luciferase reporter gene construct transfected into a m...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-02, Vol.95 (4), p.1387-1391
Main Authors: Brenza, Holly L., Kimmel-Jehan, Christine, Jehan, Frederic, Shinki, Toshimasa, Wakino, Shu, Anazawa, Hideharu, Suda, Tatsuo, DeLuca, Hector F.
Format: Article
Language:English
Subjects:
Biochemistry
Biological Sciences
Cell lines
Complementary DNA
Genes
Hormones
Kidney cells
Nucleotides
Oligonucleotides
Reporter genes
Vitamin D
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Summary:The DNA flanking the 5′sequence of the mouse 1α -hydroxylase gene has been cloned and sequenced. A TATA box has been located at -30 bp and aCCAAT box has been located at -79 bp. The gene's promoter activity has been demonstrated by using a luciferase reporter gene construct transfected into a modified pig kidney cell line, AOK-B50. Parathyroid hormone stimulates this promoter-directed synthesis of luciferase by 17-fold, whereas forskolin stimulates it by 3-fold. The action of parathyroid hormone is concentration-dependent. 1,25-Dihydroxyvitamin D3does not suppress basal promoter activity and marginally suppresses parathyroid hormone-driven luciferase reporter activity. The promoter has three potential cAMP-responsive element sites, and two perfect and one imperfect AP-1 sites, while no DR-3 was detected. These results indicate that parathyroid hormone stimulates 25-hydroxyvitamin D3-1α -hydroxylase by acting on the promoter of the 1α -hydroxylase gene.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.4.1387