ArticleMolecular and cellular biology1996
The activity of the highly inducible mouse phenylalanine hydroxylase gene promoter is dependent upon a tissue-specific, hormone-inducible enhancer.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 42 citations in OpenAlex.
- Low-Dose Gene Therapy for Murine PKU Using Episomal Naked DNA Vectors Expressing PAH from Its Endogenous Liver Promoter.Molecular therapy. Nucleic acids · 2017Article
- Gender dimorphism in aspartame-induced impairment of spatial cognition and insulin sensitivity.PloS one · 2012Article
- Metabolomics identifies novel Hnf1alpha-dependent physiological pathways in vivo.Molecular endocrinology (Baltimore, Md.) · 2010Article
- Induction of human UGT1A1 by a complex of dexamethasone-GR dependent on proximal site and independent of PBREM.Molecular biology reports · 2008Article
- Induction of human UDP-glucuronosyltransferase 1A1 by cortisol-GR.Molecular biology reports · 2006Article
- Cloning and characterization of the human beta2-glycoprotein I (beta2-GPI) gene promoter: roles of the atypical TATA box and hepatic nuclear factor-1alpha in regulating beta2-GPI promoter activity.The Biochemical journal · 2004Article
- The Nuclear Factor I (NFI) gene family in mammary gland development and function.Journal of mammary gland biology and neoplasia · 2003Review
- An enhancer element 6 kb upstream of the mouse HNF4alpha1 promoter is activated by glucocorticoids and liver-enriched transcription factors.Nucleic acids research · 2001Article
- Embryonic but not postnatal reexpression of hepatocyte nuclear factor 1alpha (HNF1alpha) can reactivate the silent phenylalanine hydroxylase gene in HNF1alpha-deficient hepatocytes.Molecular and cellular biology · 2001Article
- Hepatocyte nuclear factor-1 acts as an accessory factor to enhance the inhibitory action of insulin on mouse glucose-6-phosphatase gene transcription.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- 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.Proceedings of the National Academy of Sciences of the United States of America · 1998Article
- Studies on the enzymatic and transcriptional activity of the dimerization cofactor for hepatocyte nuclear factor 1.Proceedings of the National Academy of Sciences of the United States of America · 1997Article
- Hepatocyte nuclear factor 1alpha gene inactivation impairs chromatin remodeling and demethylation of the phenylalanine hydroxylase gene.Molecular and cellular biology · 1997Article
- Hepatocyte nuclear factor 4 expression overcomes repression of the hepatic phenotype in dedifferentiated hepatoma cells.Molecular and cellular biology · 1997Article
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression of the phenylalanine hydroxylase gene in livers and kidneys of rodents is activated at birth and is induced by glucocorticoids and cyclic AMP in the liver. Regulatory elements in a 10-kb fragment upstream of the mouse gene have been characterized. The promoter lacks TAATA and CCAAT consensus sequences and shows only extremely weak activity in transitory expression assays with phenylalanine hydroxylase-producing hepatoma cells. No key elements for regulation of promoter activity are localized within 2 kb of upstream sequences. However, a liver-specific DNase I-hypersensitive site at kb -3.5 comprises a tissue-specific and hormone-inducible enhancer. This enhancer contains multiple protein binding sites, including sites for ubiquitous factors (NF1 and AP1), the glucocorticoid receptor, and the hepatocyte-enriched transcription factors hepatocyte nuclear factor 1 (HNF1) and C/EBP. Mutation revealed that the last two sites are critical not only for basal activity but also for obtaining a maximal hormone response. Efficient transcription from the highly inducible promoter shows absolute dependence upon the enhancer at kb - 3.5, which in turn requires HNF1 and C/EBP as well as hormones. The regulatory region of the mouse phenylalanine hydroxylase gene differs totally from that of humans, even though the genes of both species are expressed essentially in the liver. Furthermore, the phenylalanine hydroxylase gene of mice shows an expression pattern very similar to those of the rodent tyrosine aminotransferase and phosphoenolpyruvate carboxykinase genes, yet each shows a different organization of its regulatory region.
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