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Functional characterization of a unique liver gene promoter.

Publication ,  Journal Article
Wang, Y; Hahn, TM; Tsai, SY; Woo, SL
Published in: J Biol Chem
March 25, 1994

Human phenylalanine hydroxylase (PAH) is specifically expressed in the liver to convert L-phenylalanine to L-tyrosine. Deficiency of the PAH enzyme causes classic phenylketonuria, a common genetic disorder. The human PAH gene has a TATA-less promoter with multiple transcriptional initiation sites. A 9-kilobase DNA fragment 5'-flanking to the human PAH gene is sufficient to confer tissue- and developmental stage-specific expression of a reporter gene in transgenic mice. Deletion studies showed that the -121-base pair proximal promoter still retained a significant level of activity in hepatic cells. At least two protein binding sites, PAH-A and PAH-B, were identified in the proximal region of the human PAH promoter using rat liver nuclear extract. The PAH-A site covers a unique palindromic sequence, and the PAH-B site contains CCCTCCC repeats. Both elements are ubiquitous and essential regulatory elements for transcriptional activity. Nuclear protein factors that bind to the PAH-A and -B sites are detected in different cell types and are distinct from previously characterized transcription factors. No tissue-specific transcription factor binding sites have been detected within the proximal promoter region of the human PAH gene. These results suggest that the PAH gene promoter has a unique organization of regulatory elements for its tissue-specific expression in comparison with other liver gene promoters.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

March 25, 1994

Volume

269

Issue

12

Start / End Page

9137 / 9146

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Sequence Deletion
  • Promoter Regions, Genetic
  • Phenylalanine Hydroxylase
  • Nuclear Proteins
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Liver
  • Humans
  • DNA-Binding Proteins
 

Citation

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MLA
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Wang, Y., Hahn, T. M., Tsai, S. Y., & Woo, S. L. (1994). Functional characterization of a unique liver gene promoter. J Biol Chem, 269(12), 9137–9146.
Wang, Y., T. M. Hahn, S. Y. Tsai, and S. L. Woo. “Functional characterization of a unique liver gene promoter.J Biol Chem 269, no. 12 (March 25, 1994): 9137–46.
Wang Y, Hahn TM, Tsai SY, Woo SL. Functional characterization of a unique liver gene promoter. J Biol Chem. 1994 Mar 25;269(12):9137–46.
Wang, Y., et al. “Functional characterization of a unique liver gene promoter.J Biol Chem, vol. 269, no. 12, Mar. 1994, pp. 9137–46.
Wang Y, Hahn TM, Tsai SY, Woo SL. Functional characterization of a unique liver gene promoter. J Biol Chem. 1994 Mar 25;269(12):9137–9146.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

March 25, 1994

Volume

269

Issue

12

Start / End Page

9137 / 9146

Location

United States

Related Subject Headings

  • Structure-Activity Relationship
  • Sequence Deletion
  • Promoter Regions, Genetic
  • Phenylalanine Hydroxylase
  • Nuclear Proteins
  • Mutagenesis, Site-Directed
  • Molecular Sequence Data
  • Liver
  • Humans
  • DNA-Binding Proteins