Oestrogen and glucocorticoid responsive elements are closely related but distinct

Klöck, Gerd; Strähle, Uwe; Schütz, Günther

doi:10.1038/329734a0

Cited by 349 publications

(148 citation statements)

References 15 publications

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“…Interestingly, estradiol has no effect on expression in MCF7 cells, even though this cell line possesses sufficient amounts of the estradiol receptor to allow induction of estrogen-responsive marker genes to occur (10,16). Plasmids in which the hexanucleotide sequence TGTTCT in both halves of the palindrome has been changed to TGACCT allow induction by estradiol, but not by dexamethasone, suggesting that estradiol regulation requires a related but distinct sequence (24). The absence of any effect by the other steroids-in particu- induction.…”

Section: Resultsmentioning

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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Section: Resultsmentioning

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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“…In intron 3, the latter half (underlined) of the sequence TGGCTGTCTACAC-AGCCCTTGCATGATGTTCT is consistent with a glucocorticoid regulatory element (consensus TGTTCT, cf. its optimized palindrome AGAACANNNTGTTCT; Klock et al, 1987) and is very like a glucocorticoid regulatory element of the rat tryptophan oxidase gene (CTTTCATGATGTCCT; Danesch et al, 1987). The adjacent sequence TGGCTGTCTACACAGCC is a perfect palindrome (underlined) with a spacer tetranucleotide ('hyphen'), CTAC, separating the elements.…”

Section: Gstmu3mentioning

confidence: 99%

Structure of human glutathione S-transferase class Mu genes

Taylor¹,

Oliver²,

Sherrington³

et al. 1991

Biochemical Journal

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Nucleotide sequencing of a human cosmid clone shows that the exon-intron structures of a glutathione S-transferase multigene family are conserved between man and rat, that the human gene family is clustered and that gene conversion events have occurred within the cluster. In addition, between man and rat, there is a high degree of nucleotide sequence identity not only in exons but also in some introns. These conserved sequences are coincident with homologous sequences subject to gene conversion in both species, and hence the utilization of gene conversion by this gene family has itself been conserved. By using transient-expression assay the conserved/converted regions are shown to be capable of modulating transcriptional activity. The data suggest that DNA repair by gene conversion may be a chemical immunity mechanism. which could result in acquired resistance to toxins and, in particular, drug resistance due to glutathione S-transferase in tumours.

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“…Prior to experiments, cells were placed for 24 h in medium without phenol red containing 10% charcoal-stripped serum. For assays of ER activity, 2610 5 cells were transfected with 0.5 mg of the ERE-tk-luc construct (Klock et al, 1987) and various expression vectors. For each transfection, the total quantity of transfected plasmid DNA was kept constant by the addition of pcDNA3 plasmid (Invitrogen).…”

Section: Transient Transfectionmentioning

confidence: 99%

Transcriptional activation by the oestrogen receptor α is modulated through inhibition of cyclin-dependent kinases

et al. 2002

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We have investigated the interaction between the expression of p21 WAF1/CIP1/SDI1 , a stoichiometric inhibitor of Cdk, and the transcriptional activity of the oestrogen receptor a (ERa). Transient transfection experiments demonstrated that the expression of p21 WAF1/CIP1/SDI1 amplified the transcriptional activation by ERa. A dominant negative mutant of Cdk2 also enhanced the ERa transcriptional activity, indicating that the underlying mechanism relies on the inhibition of Cdk2 activity and cell cycle arrest. In agreement with this conclusion, experiments with p21 WAF1/CIP1/SDI1 mutants demonstrated that the domain involved in the binding of p21 WAF1/CIP1/SDI1 to Cdks was indispensable for the modulation of ERa activity. In addition, we show that expression of p21 WAF1/CIP1/SDI1 alleviates the block on CBP function mediated by Cdk2 and in turn stimulates transcriptional activation by ERa in a CBPhistone acetyltransferase (HAT)-dependent manner. These results suggest a novel mechanism by which p21 WAF1/CIP1/SDI1 functions as an enhancer of ERa activity through the modulation of CBP function.

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Oestrogen and glucocorticoid responsive elements are closely related but distinct

Cited by 349 publications

References 15 publications

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

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

Structure of human glutathione S-transferase class Mu genes

Transcriptional activation by the oestrogen receptor α is modulated through inhibition of cyclin-dependent kinases

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