Activation of phenylalanine hydroxylase expression following genomic DNA transfection of hepatoma cells

Faust, Daniela M.; Imaizumi-Scherrer, Tereza; Fulchignoni-Lataud, Marie-Claude; Catherin, Anne-Marie; Iost, Isabelle; Weiss, Mary C.

doi:10.1111/j.1432-0436.1990.tb00539.x

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…Screening of a genomic BALB/c mouse DNA library in -EMBL3 (Clontech) with a 0.45-kb NcoI-PvuII restriction fragment of the 5Ј part of the cDNA coding for mouse PAH (pmPAH20 [22]) resulted in isolation of clone -17, which included 15 kb of sequences upstream of exon 1. Fragments were subcloned into M13tg130/131 (Amersham) or pBluescript KSII (Stratagene) by standard protocols.…”

Section: Methodsmentioning

confidence: 99%

The Activity of the Highly Inducible Mouse Phenylalanine Hydroxylase Gene Promoter Is Dependent upon a Tissue-Specific, Hormone-Inducible Enhancer

Faust

Catherin

Barbaux

et al. 1996

Molecular and Cellular Biology

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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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Section: Methodsmentioning

confidence: 99%

The Activity of the Highly Inducible Mouse Phenylalanine Hydroxylase Gene Promoter Is Dependent upon a Tissue-Specific, Hormone-Inducible Enhancer

Faust

Catherin

Barbaux

et al. 1996

Molecular and Cellular Biology

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show abstract

“…Preliminary experiments with Hep -5A -01, Hep -EBNA-2 and FAGl suggest that the frequency of revertants is about l o w 6 under normal growth conditions. Such a stability will be reinforced with hormonal supplements [20] and should accomodate experiments aimed at the cloning of extinguishing genes for the urea cycle [4, 291.…”

Section: Discussionmentioning

confidence: 79%

Selection of variant hepatoma cells in liver-specific growth media: regulation at the mRNA level

et al. 1992

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Gene expression in hepatocyte-like lines established by targeted carcinogenesis in transgenic mice

Antoine

Levrat

Vallet

et al. 1992

Experimental Cell Research

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Activation of phenylalanine hydroxylase expression following genomic DNA transfection of hepatoma cells

Cited by 4 publications

References 34 publications

The Activity of the Highly Inducible Mouse Phenylalanine Hydroxylase Gene Promoter Is Dependent upon a Tissue-Specific, Hormone-Inducible Enhancer

The Activity of the Highly Inducible Mouse Phenylalanine Hydroxylase Gene Promoter Is Dependent upon a Tissue-Specific, Hormone-Inducible Enhancer

Selection of variant hepatoma cells in liver-specific growth media: regulation at the mRNA level

Gene expression in hepatocyte-like lines established by targeted carcinogenesis in transgenic mice

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