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Identification of hepatic nuclear factor 1 binding sites in the 5' flanking region of the human phenylalanine hydroxylase gene: implication of a dual function of phenylalanine hydroxylase stimulator in the phenylalanine hydroxylation system.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lei, Xiulan Kaufman, Seymour |
| Copyright Year | 1998 |
| Abstract | Phenylalanine hydroxylase stimulator (PHS) is a component of the phenylalanine hydroxylation system that is involved in the regeneration of the cofactor tetrahydrobiopterin. It is also identical to the dimerization cofactor of hepatocyte nuclear factor 1 (HNF1) (DCoH) that is able to enhance the transcriptional activity of HNF1. Moreover, it has the structural potential for binding macromolecules such as proteins and nucleic acids, consistent with its involvement in gene expression. We investigated whether PHS/DCoH could enhance the expression of phenylalanine hydroxylase (PAH). Cotransfection assays showed that DCoH itself could not transactivate the 9-kb human PAH 5' flanking fragment. However, this 9-kb fragment was transactivated by HNF1 in a dose-dependent manner with a maximum of nearly 8-fold activation; DCoH potentiated this transactivation by another 1.6-fold. The HNF1 binding sites were located at -3.5 kb in a region that is 77.5% identical to the mouse liver-specific hormone-inducible PAH gene enhancer. This study suggests a possible dual function of PHS in vivo in the human phenylalanine hydroxylation system: it is involved in the regeneration of the cofactor tetrahydrobiopterin and can also enhance the expression of the human PAH gene. |
| Starting Page | 1 |
| Ending Page | 4 |
| Page Count | 4 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.pnas.org/content/95/4/1500.full.pdf |
| PubMed reference number | 9465044v1 |
| Volume Number | 95 |
| Issue Number | 4 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Binding Sites Cell Nucleus Dual Flank (surface region) Gene Expression HNF1A gene Hepatocyte Nuclear Factor 1 Hepatocyte Nuclear Factors Hydroxylation Melphalan Mixed Function Oxygenases NFI Transcription Factors Natural regeneration Nucleic Acids PCBD1 gene Phenylalanine Hydroxylase Tetrahydrobiopterin Trans-Activation, Genetic Transcription, Genetic chemical cofactor iron-sulfur-molybdenum cofactor biosynthetic process macromolecule |
| Content Type | Text |
| Resource Type | Article |
