Mutation analysis of HNF-4 binding sites in the human glucose-6-phosphatase promoter

  • Authors:
    • Keiko Hirota
    • Hisanori Aoyama
    • Akiyoshi Fukamizu
  • View Affiliations

  • Published online on: March 1, 2005     https://doi.org/10.3892/ijmm.15.3.487
  • Pages: 487-490
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Abstract

HNF-4, a member of the nuclear receptor superfamily, binds to HNF-4 response elements (HRE), consisting of a direct repeat of the hexameric half-sites spaced by 1 nt (direct repeat 1) and activates a number of genes, which play central roles in fatty acids and glucose metabolism. Glucose-6-phosphatase (G6Pase) catalyzes the terminal step in the gluconeogenic and glycogenolytic pathways. A previous study has shown that HNF-4 binds to two DR1s in the regions A (located between −266 and −234) and B (located between −306 and −274) on the human G6Pase promoter. We found that the region B contains the one more DR1 element, composed of the two half-sites, designated half-sites a and b, the latter of which overlaps with the previously identified DR1 consisting of two half-sites, designated half-sites b and c. In this study, electrophoretic mobility shift assay (EMSA) using point mutations in each half-site a, b, or c indicated that HNF-4 binds to the combination of half-sites a and b, but not to half-sites b and c. Furthermore, mutational analysis demonstrated that, in the context of the human G6Pase promoter, the half-sites a and b, but not the half-sites b and c, are required for the stimulatory effect of HNF-4. These results suggested that the DR1 element containing the half-sites a and b is a functional HRE that mediates the induction of hG6Pase promoter activity by HNF-4.

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March 2005
Volume 15 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Hirota K, Aoyama H and Fukamizu A: Mutation analysis of HNF-4 binding sites in the human glucose-6-phosphatase promoter. Int J Mol Med 15: 487-490, 2005
APA
Hirota, K., Aoyama, H., & Fukamizu, A. (2005). Mutation analysis of HNF-4 binding sites in the human glucose-6-phosphatase promoter. International Journal of Molecular Medicine, 15, 487-490. https://doi.org/10.3892/ijmm.15.3.487
MLA
Hirota, K., Aoyama, H., Fukamizu, A."Mutation analysis of HNF-4 binding sites in the human glucose-6-phosphatase promoter". International Journal of Molecular Medicine 15.3 (2005): 487-490.
Chicago
Hirota, K., Aoyama, H., Fukamizu, A."Mutation analysis of HNF-4 binding sites in the human glucose-6-phosphatase promoter". International Journal of Molecular Medicine 15, no. 3 (2005): 487-490. https://doi.org/10.3892/ijmm.15.3.487