Isolation and characterization of the rat tryptophan oxygenase gene.

Schmid, Wolfgang; Scherer, Gerd; Danesch, Ulrich; Zentgraf, Hanswalter; Matthias, Patrick; Strange, Carolyn M.; Röwekamp, Walter; Schütz, Günther

doi:10.1002/j.1460-2075.1982.tb00026.x

Cited by 65 publications

(23 citation statements)

References 46 publications

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“…1). The localization of polII of adult hepatocytes is consistent with the results of Northern blotting showing that the downstream TATA box is more important for transcription (Schmid et al 1982). From the ratio of the precipitated/input DNA ( Fig.…”

Section: Resultssupporting

confidence: 87%

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GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes

Kaneoka¹,

Miyake²,

Iijima³

2008

Cytotechnology

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The glucocorticoid receptor regulates liver-specific expression of the tryptophan oxygenase gene through glucocorticoid responsive elements located -0.45 and -1.2 kb from the transcription start site. However, the hormone-mediated induction is restricted to adult hepatocytes, and fetal hepatocytes are unable to express the gene even in the presence of the receptor and glucocorticoid hormone. The difference in sensitivity to the hormone between adult and fetal hepatocytes has not been well understood. In this study, we analyzed the structure of the tryptophan oxygenase gene's promoter. The promoter has two TATA boxes, and transcription starts from the downstream TATA box. We found that a transcription factor GATA4 bound to the downstream TATA box and may inhibit the binding of TATA-binding protein, resulting in transcriptional repression even in the presence of glucocorticoid in fetal hepatocytes.

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Section: Resultssupporting

confidence: 87%

“…Furthermore, this gene has two TATA-like sequences, which are close together, just 180 bp apart, in the promoter region (Schmid et al 1982). However, the function of the tandem TATA sequences in the regulation of the TO gene has not yet been clear.…”

Section: Introductionmentioning

confidence: 99%

GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes

Kaneoka¹,

Miyake²,

Iijima³

2008

Cytotechnology

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“…Furthermore, the search does not show exact matches with full or partial sequences of genes known to be regulated by glucocorticoids, including rat growth hormone (30,31), rat tryptophan oxygenase (32), rabbit uteroglobin (33), and human proopiomelanocortin (34). We conclude that this simple consensus sequence is not complete enough for predicting sites in uncharacterized genes.…”

Section: ' T-t-t-g-g-g-c-a-c-a-a-t-g-t-c-t-c-c-t-g-mentioning

confidence: 83%

The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor.

Moore¹,

Marks²,

Buckley³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

198

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Glucocorticoid receptor (GCR) protein stimulates transcription from a variety of cellular genes. We show here that GCR partially purified from rat liver binds specifically to a site within the first intron of the human growth hormone (hGH) gene, "100 base pairs downstream from the start of hGH transcription. GCR binding is selectively inhibited by methylation of two short, symmetrically arranged clusters of guanine residues within this site. A cloned synthetic 24-basepair deoxyoligonucleotide containing the predicted GCR binding sequence interacts specifically with GCR. The hGH binding site shares sequence homology with a GCR binding site upstream from the human metallothionein II gene and a subset of GCR binding sites from mouse mammary tumor virus. All of these binding sites for this eukaryotic transcriptional regulatory protein show remarkable similarity in overall geometry to the binding sites for several prokaryotic transcriptional regulatory proteins.Steroid hormones regulate the expression of a large number of genes in a variety of cell types. In cell lines derived from liver, for example, the amount of up to 1% of the proteins detected by two-dimensional electrophoresis is significantly altered by addition of glucocorticoids (1). In general, this regulatory activity has been attributed to direct effects of the activated glucocorticoid receptor (GCR) protein on gene expression. A number of studies have shown that the cytosolic GCR, after binding the hormone and undergoing a modification termed activation, migrates to the nucleus and binds to chromatin and perhaps to other nuclear components (2).In a few instances, the effect of steroids on the expression of individual genes has been examined in detail. In expression units as divergent as rat growth hormone, Xenopus vitellogenin, and mouse mammary tumor virus (MMTV) (3-6), addition of steroid hormones results in a rapid rise in the rate of transcription. The DNA sequences responsible for induction of MMTV transcription have been investigated by two quite different approaches. Purified activated GCR has been shown to bind specifically to several sites in a segment adjacent to the MMTV promoter as well as to several sites within the MMTV provirus (7)(8)(9)(10)(11)(12)(13). A series of gene transfer experiments have shown also that the binding sites in the promoter region are sufficient to direct steroid inducibility in vivo (14)(15)(16)(17)(18)(19)(20).We demonstrate here that the human growth hormone (hGH) gene contains a specific binding site for activated, partially purified rat liver GCR. This site is similar in sequence to a subset of the MMTV binding sites near the promoter and to a binding site upstream from the human metallothionein II (hMTII) promoter (21), allowing prediction of a consensus sequence for a simple type of GCR binding site. The hGH site is markedly different from the MMTV and hMTII sites in position, however, being centered 100 base pairs (bp) downstream (3') from the start of transcription, within the first intron of the hGH ...

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“…This probe fragment (0.04 pmol) was mixed in 10 ul of hybridization solution with total RNA isolated from mouse Ltk-cells 21 hr after transfection with mutant allele RHS1A (40 Mg of RNA) or normal TAT allele (20 Mg of RNA) or from untransfected cells (20 Mg of RNA). Hybridization and nuclease S1 digestion were essentially as described (23), except that RNADNA hybrids were allowed to form at 520C for 8 hr, then at 500C for 4 hr, and finally at 480C for 4 hr.…”

Section: Methodsmentioning

confidence: 99%

Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II.

Natt

Kida

Odièvre

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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Tyrosinemia type II (Richner-Hanhart syndrome, RHS) is a disease of autosomal recessive inheritance characterized by keratitis, palmoplantar hyperkeratosis, mental retardation, and elevated blood tyrosine levels. The disease results from deficiency in hepatic tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5), a 454-amino acid protein encoded by a gene with 12 exons. To identify the causative mutations in five TAT alleles cloned from three RHS patients, chimeric genes constructed from normal and mutant TAT alleles were tested in directing TAT activity in a transient expression assay. DNA sequence analysis of the regions identified as nonfunctional revealed six different point mutations. Three RHS alleles have nonsense mutations at codons 57, 223, and 417, respectively. One "complex" RHS allele carries a GI GG splice donor mutation in intron 8 together with a Gly Val substitution at amino acid 362. A new splice acceptor site in intron 2 ofthe fifth RHS allele leads to a shift in reading frame.Tyrosinemia type II, also known as Richner-Hanhart syndrome (RHS), is an inborn error of metabolism due to a block in the transamination reaction converting tyrosine to p-hydroxyphenylpyruvate, a step catalyzed by the hepatic cytosolic enzyme tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5). RHS patients suffer from keratitis, palmar and plantar hyperkeratosis, and sometimes mental retardation, accompanied by highly elevated serum and urine levels of tyrosine and its metabolites. The condition improves rapidly on a tyrosine-and phenylalanine-restricted diet (for reviews see refs. 1 and 2).TAT has been extensively studied in rat and mouse, revealing a complex pattern of regulation. Enzyme activity is virtually absent in fetal rat liver and becomes detectable just after birth (3). The TAT gene is under hormonal control by glucocorticoids and cAMP, which increase the basal transcription rate 5-to 10-fold (4, 5), acting via different response elements in the 5' flanking region of the gene (6, 7). Furthermore, the rodent TAT genes are subject to two trans-acting regulators. Basal expression and hormone inducibility of the Tat gene on mouse chromosome 8 are controlled by a positive trans-acting factor, alf, encoded on mouse chromosome 7 (8). Conversely, the tissue-specific extinguisher locus Tse-J on mouse chromosome 11 encodes a product that represses Tat gene transcription in nonliver cells (9).Little is known about the regulation of the human TAT gene. As in rodents, hepatic TAT activity reaches significant levels shortly after birth, although some activity is present in the fetus (10). Induction of human TAT by glucocorticoids and cAMP has been demonstrated in fetal liver organ cultures (11). Moreover, there is evidence for a Tse-1-like factor on human chromosome 17 (9).The human TAT gene extends over 10.9 kilobases (kb) containing 12 exons, and its 3.0-kb mRNA codes for a 454-amino acid protein of 50.4 kDa (12). We previously described an RHS ...

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Isolation and characterization of the rat tryptophan oxygenase gene.

Cited by 65 publications

References 46 publications

GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes

GATA4 inhibits expression of the tryptophan oxygenase gene by binding to the TATA box in fetal hepatocytes

The first intron of the human growth hormone gene contains a binding site for glucocorticoid receptor.

Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II.

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