Parathyroid hormone activation of the 25-hydroxyvitamin D3-1alpha-hydroxylase gene promoter

The DNA flanking the 5' sequence of the mouse 1alpha-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...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1998-02, Vol.95 (4), p.1387
Main Authors: Brenza, H L, Kimmel-Jehan, C, Jehan, F, Shinki, T, Wakino, S, Anazawa, H, Suda, T, DeLuca, H F
Format: Article
Language:English
Subjects:
25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics
Animals
Base Sequence
Cloning, Molecular
Colforsin - pharmacology
Cyclic AMP - pharmacology
Dose-Response Relationship, Drug
Enzymes
Gene Expression Regulation, Enzymologic - drug effects
Genes
Hormones
Metabolism
Mice
Molecular Sequence Data
Parathyroid Hormone - pharmacology
Promoter Regions, Genetic
Signal Transduction
Transcription, Genetic - drug effects
Vitamin D
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Summary:The DNA flanking the 5' sequence of the mouse 1alpha-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 D3 does 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 D3-1alpha-hydroxylase by acting on the promoter of the 1alpha-hydroxylase gene.
ISSN:0027-8424
1091-6490