The nucleotide sequences recognized by the glucocorticoid receptor in the rabbit uteroglobin gene region are located far upstream from the initiation of transcription.

Cato, Andrew C. B.; Geisse, Sabine; Wenz, Michael; Westphal, Hannes M.; Beato, Miguel

doi:10.1002/j.1460-2075.1984.tb02208.x

Cited by 116 publications

(48 citation statements)

References 28 publications

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“…The GREs whose activities have been documented previously are located in the 5'-flanking regions of the inducible genes. The distance from the transcription initiation site varies from about 50 nucleotides in the case of the chicken lysozyme gene (26) to more than 2,600 nucleotides in the rabbit uteroglobin gene (3 (1,8,25).…”

Section: '-E G Gc a C A A T G T G T C C T-3' +107mentioning

confidence: 99%

Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene.

Slater¹,

Rabenau²,

Karin³

et al. 1985

Mol. Cell. Biol.

239

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In this study DNA-binding and gene transfer experiments were performed to examine a potential glucocorticoid regulatory element (GRE) in the human growth hormone gene. As assayed by nitrocellulose filter binding, only two regions of the human growth hormone gene, the 5'-flanking sequences and a fragment containing part of the first intron, were retained preferentially by purified glucocorticoid-receptor complexes. The relative binding by the transcribed sequences was three times greater than the relative binding by the 5'-flanking sequences, but less than the relative binding by a fragment containing the human metallothionein-IA gene GRE. The intron, but not the 5'-flanking sequences, generated a "footprint" when the receptor complex was used to protect the segments against exonuclease III digestion; the protected sequence spanned nucleotides +86 to +115 In the first intron and contained a structure homologous in 14 of 16 nucleotides to a 16-nucleotide consensus GRE. The hexanucleotide 5'-TGTCCT-3', thought to be important for GRE activity, not only was found in this sequence and in the 5'-flanking region, but also was present twice in the 3' end of the gene that did not show specific receptor binding. The latter results suggest that the hexanucleotide alone is not sufficient to generate specific receptor binding tight enough to be assayed in this way. To test the biological activity of the intron binding site, a fragment containing these sequences was fused 5' to the human metallothionein-IIA gene promoter depleted of its GRE and linked to the structural sequences of the herpes simplex virus thymidine kinase (TK) gene. When this hybrid gene was transfected into Rat 2 TK-cells, its expression was induced threefold by the glucocorticoid dexamethasone, as assessed by transfection efficiency and RNA blotting analyses. Expression of the same gene without the human growth hormone gene segment was not affected by the steroid, whereas the wild-type human metallothionein-IIA gene promoter containing its GRE responded to the hormone by a sixfold increase in thymidine kinase mRNA. These results indicate that the human growth hormone gene contains a structure within its first intron that can function as a GRE.Glucocorticoids exert many of their physiological effects by modulating the expression of specific genes (for a review, see reference 30). In most cases studied these effects are at the transcriptional level. Baxter et al. (2) demonstrated that glucocorticoid-receptor complexes or proteins associated with them bind to DNA. It has been postulated that these complexes recognize specific sequences on responsive genes and affect their transcription (for reviews, see references 30 and 43). The cloning of glucocorticoid-responsive genes (6,(14)(15)(16)21) and the purification of the activated form of the receptor (39, 42) have enabled testing of this hypothesis. In vitro studies of the binding of purified receptor to cloned DNA (13,22,26,32,37) in conjunction with gene transfer studies (4, 10, 13, 26) have been used to iden...

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Section: '-E G Gc a C A A T G T G T C C T-3' +107mentioning

confidence: 99%

Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene.

Slater¹,

Rabenau²,

Karin³

et al. 1985

Mol. Cell. Biol.

239

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“…The glucocorticoid and progesterone receptors bind to similar sequences within these fragments, suggesting that the binding sites may be closely related, but distinct (5, 6). Both types of receptors also bind to partially overlapping sequences in the rabbit uteroglobin gene (7,8). These sequences, however, have not been functionally characterized.…”

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confidence: 99%

A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression.

Strähle

Klöck

Schütz

1987

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

311

126

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To defmie the recognition sequence of the glucocorticoid receptor and its relationship with that of the progesterone receptor, oligonucleotides derived from the glucocorticoid response element of the tyrosine aminotransferase gene were tested upstream of a heterologous promoter for their capacity to mediate effects of these two steroids. We show that a 15-base-pair sequence with partial symmetry is sufficient to confer glucocorticoid inducibility on the promoter of the herpes simplex virus thymidine kinase gene. The same 15-base-pair sequence mediates induction by progesterone. Point mutations in the recognition sequence affect inducibility by glucocorticoids and progesterone similarly. Together with the strong conservation of the sequence of the DNA-binding domain of the two receptors, these data suggest that both proteins recognize a sequence that is similar, if not the same.The effect of steroid hormones on specific gene transcription is mediated by receptors to which the hormones bind with high selectivity and affinity. Activation of transcription results from binding of the hormone-receptor complex to specific sequences of inducible genes (1, 2). Surprisingly, it has been observed that fragments of the chicken lysozyme gene and of the long terminal repeat of mouse mammary tumor virus that confer glucocorticoid inducibility also allow progesterone induction (3, 4). The glucocorticoid and progesterone receptors bind to similar sequences within these fragments, suggesting that the binding sites may be closely related, but distinct (5, 6). Both types of receptors also bind to partially overlapping sequences in the rabbit uteroglobin gene (7,8). These sequences, however, have not been functionally characterized. To define the sequence requirements for specific binding of the glucocorticoid receptor and to determine the degree to which this sequence overlaps with the recognition sequence for the progesterone receptor, a minimal glucocorticoid response element (GRE) 15 base pairs (bp) in length was defined. This 15-bp sequence is part of the GRE region of the tyrosine aminotransferase (TAT) gene protected against DNase I digestion by the purified glucocorticoid receptor (9). We demonstrate here that the same 15-mer which confers responsiveness to glucocorticoids also mediates progesterone induction. Since point mutations in this 15-bp sequence affect inducibility by both steroids similarly, we suggest that the recognition sequences of the glucocorticoid and progesterone receptors are similar, if not identical. MATERIALS AND METHODSPlasmid Constructions. Oligonucleotides were prepared with an Applied Biosystems 380A DNA synthesizer and purified as recommended by the manufacturer. Annealing of the complementary strands, which generated BamHI or Xba I cohesive ends, and cloning upstream of the herpes simplex virus thymidine kinase (TK) promoter in pBLCAT2 (10) were done by standard procedures (11). pBLCAT2 contains the complete TK promoter (-105 to +62) linked to the chloramphenicol acetyltransferase (CAT) co...

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“…Glucocorticoids can modulate gene expression through direct binding of an activated receptor-hormone complex to the gene region (for a review, see reference 44). A consensus DNA sequence has been identified in the regions where the glucocorticoid receptor complex binds by analysis of a number of regulated genes, including mouse mammary tumor virus (32), lysozyme (34), uteroglobin (6), metallothionein-II (23), and tyrosine aminotransferase (22). Consensus sequences have also been identified in the promoter regions of the mouse and human amylase genes (11,15,31).…”

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confidence: 99%

Glucocorticoid and developmental regulation of amylase mRNAs in mouse liver cells.

et al. 1988

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We characterized alpha-amylase expression in the hepatoma cell line Hepa 1-6 and in normal mouse liver. Both Amy-1 and Amy-2 were expressed in Hepa 1-6 and were regulated by glucocorticoids. Transcription in the hepatoma cells was initiated at the same start sites as in mouse tissues. Glucocorticoid treatment increased the abundance of Amy-1 and Amy-2 transcripts by 10 to 20-fold. This increase was detected within 4 h and was maximal by 24 h. The pattern of amylase expression in this hepatoma cell line accurately reflects amylase expression in the liver in vivo. During liver development, we observed a large increase in the abundance of Amy-1 transcripts just before birth, at a time when circulating glucocorticoids are also elevated. Adult mouse liver expressed Amy-1 and Amy-2 at levels comparable to those of fully induced hepatoma cells. Liver is thus a likely source of both amylase isozymes in mouse serum. These studies demonstrate that Amy-2 expression is not limited to the pancreas but also occurs at a low level in liver cells.

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The nucleotide sequences recognized by the glucocorticoid receptor in the rabbit uteroglobin gene region are located far upstream from the initiation of transcription.

Cited by 116 publications

References 28 publications

Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene.

Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene.

A DNA sequence of 15 base pairs is sufficient to mediate both glucocorticoid and progesterone induction of gene expression.

Glucocorticoid and developmental regulation of amylase mRNAs in mouse liver cells.

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