Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.1.99.3 (PRE)
1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian ribosomal RNA gene promoters exhibit a conserved sequence between positions +1 and +16 that shows a high degree of homology to the response element for glucocorticoids and progestins (GRE/PRE). These sequences bind specifically the glucocorticoid receptor and the progesterone receptor (PR) albeit with lower affinity than a canonical GRE/PRE. Because steroid hormones are known to affect expression of the ribosomal genes, we tested the influence of hormone receptors on the activity of the ribosomal RNA gene promoter in a cell-free transcription assay. Preparations of PR that induce transcription from the mouse mammary tumour virus (MMTV) promoter do not stimulate but slightly inhibit transcription from the ribosomal RNA gene promoter. This weak negative effect is not mediated through binding to the hypothetical GRE/PRE as a mutant promoter that does not bind receptor is equally repressed. Introduction of the functional MMTV GRE/PRE upstream of the basal ribosomal RNA gene promoter does not enhance its transcription in the presence of an active PR. Thus, RNA polymerase I transcription cannot be stimulated in vitro by cis elements and regulatory proteins that are active in RNA polymerase II transcription.
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PMID:Neither the endogenous nor a functional steroid hormone receptor binding site transactivate the ribosomal RNA gene promoter in vitro. 191 32

The glucocorticoid receptor (GR) and the progestin receptor (PR) bind specifically to a variety of DNA sequences, glucocorticoid/progestin response elements (GRE/PRE), located in the proximity of responsive gene promoters. Using the isolated recombinant GR DNA-binding domain (DBD), it has recently been shown that GR interacts with the GRE/PRE, a 15-basepair partially palindromic consensus sequence, as a dimer. In this study an investigation into the GR-GRE/PRE and PR-GRE/PRE interaction has been performed using missing base contact analysis with the tyrosine aminotransferase GREII (TATII) and recombinant GR DBD as well as a fusion protein consisting of the PR DBD fused to Staph. aureus protein-A. GR and PR had identical base contact points, localized within two consecutive major grooves, binding to the same face of the DNA. Ethylation interference was also performed on the GR DBD-TATII interaction. The contact points with the backbone phosphate groups flank the contacts within the major groove for each of the two half-sites. Knowledge of the contact points within the DNA sequence together with the three-dimensional structure of the protein enables modelling of the protein-DNA interaction.
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PMID:Identification of protein contact sites within the glucocorticoid/progestin response element. 192 92

Steroid hormone receptors can be divided into two subfamilies according to the structure of their DNA binding domains and the nucleotide sequences which they recognize. The glucocorticoid receptor and the progesterone receptor (PR) recognize an imperfect palindrome (glucocorticoid responsive element/progesterone responsive element [GRE/PRE]) with the conserved half-sequence TGTYCY, whereas the estrogen receptor (ER) recognizes a palindrome (estrogen responsive element) with the half-sequence TGACC. A series of symmetric and asymmetric variants of these hormone responsive elements (HREs) have been tested for receptor binding and for the ability to mediate induction in vivo. High-resolution analysis demonstrates that the overall number and distribution of contacts with the N-7 position of guanines and with the phosphate backbone of various HREs are quite similar for PR and ER. However, PR and glucocorticoid receptor, but not ER, are able to contact the 5'-methyl group of thymines found in position 3 of HREs, as shown by potassium permanganate interference. The ER mutant HE84, which contains a single amino acid exchange, Glu-203 to Gly, in the knuckle of ER, creates a promiscuous ER that is able to bind to GRE/PREs by contacting this thymine. Elements with the sequence GGTCAcagTGTYCT that represent hybrids between an estrogen response element and a GRE/PRE respond to estrogens, glucocorticoids, and progestins in vivo and bind all three wild-type receptors in vitro. These hybrid HREs could serve to confer promiscuous gene regulation.
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PMID:Functional interaction of hybrid response elements with wild-type and mutant steroid hormone receptors. 203 29

The structure of the 42-kilobase (kb) long chicken progesterone receptor (cPR) gene and of all six transcripts that are detectable on Northern blots was determined. The first of 8 exons encodes the N-terminal region A/B which is highly divergent among different species and contains a constitutive transcription activation function. The DNA (DBD)- and hormone-binding domains (HBD) are assembled from 2 and 5 exons, respectively, with the individual "zinc fingers" of the DBD encoded by separate exons. In addition to the previously described 4.5-kb cPR mRNA species, alternative polyadenylation, splicing variation, and "5'-truncation" lead to the generation of 5 further mRNAs. Most importantly, this 5'-truncation produces, by an as yet unidentified mechanism, an abundant transcript which encodes form A but not form B of cPR. Lack of splicing at the exon 2 splice-donor and polyadenylation due to a signal site in the second intron generates a previously undetected 3.4-kb mRNA species. The corresponding cDNA was sequenced in its entirety and shown to encode only region A/B and the N-terminal "finger" of the DBD. Alternative polyadenylation upstream of the signal site for the 4.5-kb mRNA is responsible for the appearance of a 3.3-kb mRNA. The longest cPR mRNA (8.2 kb) originates from a transcription termination point more than 3 kb downstream of the 4.5-kb mRNA 3'-end. Finally, the primary sequence of more than 2 kb upstream sequences of the cPR gene, containing several consensus hexamer progestin/glucocorticoid receptor-binding sites (PRE/GRE and putative Sp1 binding motifs, is discussed.
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PMID:Characterization of multiple mRNAs originating from the chicken progesterone receptor gene. Evidence for a specific transcript encoding form A. 230 88

Bacterially-expressed fusion proteins containing the DNA-(region C) or hormone-binding (region E) domains of the chicken progesterone receptor (cPR) fused to the C terminus of Escherichia coli beta-galactosidase were analysed for the specificity of interaction with natural and synthetic hormone-responsive elements (HREs) and progestins, respectively. The purified fusion protein containing the progestin-binding domain bound progesterone with an apparent Kd of 1.0-1.5 nM and was specifically photocross-linked with the synthetic progestin R5020 in crude bacterial lysates. Labelling of intact bacterial cells with [3H]R5020 revealed that the majority, if not all, of the bacterially produced hormone-binding domain was active. No differences in the binding to a synthetic palindromic glucocorticoid/progestin-responsive element (GRE/PRE) were found when the bacterially produced cPR DNA-binding domain was compared in methylation interference assays with the full-length chicken progesterone receptor form A expressed in eukaryotic cells. The study of dissociation kinetics, however, revealed differences in the half-life of the complexes formed between the palindromic GRE/PRE and either the receptor form A or the fusion protein containing the cPR DNA-binding domain. DNase I protection experiments demonstrated that the bacterially produced region C of the cPR generated specific 'footprints' on the mouse mammary tumour virus long terminal repeat (MMTV-LTR) which were nearly identical to those previously reported for the rat glucocorticoid receptor.
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PMID:Expression of active hormone and DNA-binding domains of the chicken progesterone receptor in E. coli. 254 Sep 61

The glucocorticoid-progesterone responsive element (GRE/PRE) of the tyrosine aminotransferase (TAT) gene is a steroid-inducible enhancer. We show that the GRE/PRE can also work in the absence of a distal promoter element when located 5' to the ovalbumin TATA box. The GRE/PRE in this position retains progesterone or glucocorticoid receptor and hormone dependency for the induction of gene expression. Initiation of transcription occurs correctly, and induction occurs at the mRNA level. These data indicate that a steroid-inducible enhancer can function without a distal promoter element.
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PMID:A steroid response element can function in the absence of a distal promoter. 290 64

A steroid hormone responsive element (GRE/PRE), sufficient to confer glucocorticoid and progesterone inducibility when linked to a reporter gene, was used in band-shift assays to examine its molecular interactions with steroid hormone receptors. Both progesterone and glucocorticoid receptors bound directly and specifically to the GRE/PRE. The purine contact sites for both form A and form B chicken progesterone receptor, as well as those for rat glucocorticoid receptor, are identical. A peptide fragment produced in bacteria that primarily contain the DNA binding domain of the glucocorticoid receptor binds first to the TGTTCT half-site of the GRE/PRE, and a second molecule binds subsequently to the TGTACA (half-site) of the GRE/PRE in a cooperative manner. Utilizing the peptide fragment and the protein A-linked fragment, we demonstrated that the receptor interacts with its cognate enhancer as a dimer.
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PMID:Molecular interactions of steroid hormone receptor with its enhancer element: evidence for receptor dimer formation. 316 84

The effect of steroid hormones on multiplication of the human polyomavirus BK (BKV) was studied. Physiological concentrations of the synthetic glucocorticoid dexamethasone, progesterone R5020, or estrogen 17 beta-estradiol enhanced the permissivity of the host cell for BKV, resulting in an up to 11-fold (dexamethasone), 5-fold (progesterone), or 3-fold (17 beta-estradiol) higher virus yield. The increase in virus yield in dexamethasone-stimulated cells correlated with enhanced steady-state levels of viral transcripts. The late leader sequence of the BKV control region contains a hormone response unit composed of a nonconsensus glucocorticoid and/or progesterone response element (GRE/PRE) and a fully consensus estrogen response element (ERE). DNA-protein binding studies showed that the glucocorticoid receptor and the progesterone receptor bound to this BKV GRE/PRE-like sequence, while the estrogen receptor could bind to the BKV ERE motif. By transient transfection assays, we were able to show that these sequences can mediate steroid hormone-induced gene expression. However, no cooperative transactivation effect between the BKV GRE/PRE-like motif and BKV ERE motif was observed. This BKV hormone response unit may play an important role in vivo by enhancing a productive BKV infection, and perhaps also by reactivating a latent infection, during physiological or pathological conditions accompanied by increased steroid hormone levels.
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PMID:A steroid hormone response unit in the late leader of the noncoding control region of the human polyomavirus BK confers enhanced host cell permissivity. 813 26

Circular permutation analysis was used to determine the degree of DNA bending induced by binding of the glucocorticoid receptor (GR) DNA binding domain (DBD), the human progesterone receptor (PR) DBD, PR-A:A and PR-B:B homodimers, and PR-A:B heterodimers to the glucocorticoid response element/progesterone response element (GRE/PRE). The bending angles induced by the GR DBD and the PR DBD were approximately 28 degrees and 25 degrees, respectively. The PR-B:B and PR-A:A homodimers and the PR-A:B heterodimers all induced similar DNA bending angles of 72-77 degrees. The substantially greater DNA bend induced by full-length PR compared to the PR DBD indicates that sequences outside the classic zinc finger DNA binding domain may play an important role in the interaction of PR with the GRE/PRE. Because PR-A:A and PR-B:B homodimers and the PR-A:B heterodimers induce similar DNA bends, the different abilities of the PR-A and PR-B isoforms to activate transcription are not due to differences in their abilities to distort DNA structure.
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PMID:DNA bending is induced by binding of the glucocorticoid receptor DNA binding domain and progesterone receptors to their response element. 918 56

It has been shown previously that sigma receptor agonists reveal potential antidepressant activity in experimental models. Moreover, some data indicate sigma receptor contribution to stress-induced responses (e.g., conditioned fear stress in mice), though the mechanism by which sigma ligands can exert their effects, remains unclear. Recent studies have indicated that antidepressant drugs (ADs) inhibit glucocorticoid receptor (GR) function in vitro. The aim of the present study was to find out whether sigma receptor ligands are able to directly affect GR action. To this end, we evaluated the effect of sigma receptor agonists and antagonists on GR function in mouse fibroblast cells (L929) stably transfected with mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) plasmid (LMCAT cells). For this study, we chose SA4503, PRE 084, DTG (selective sigma(1) or sigma(1/2) receptor agonists) and BD 1047, SM 21, rimcazole (sigma receptor antagonists). Fluvoxamine, the selective serotonin reuptake inhibitor with sigma(1/2) receptor affinity, was used for comparison. It was found that SM 21 (at 1, 3, 10 and 30 microM), BD 1047 (3, 10 and 30 microM) rimcazole (10 microM), and fluvoxamine (at 3, 10 and 30 microM) significantly inhibited corticosterone-induced gene transcription, while DTG, SA 4503 and PRE 084 remained ineffective. Thus, the sigma receptor agonists that predominantly showed antidepressant-like activity in behavioral models, were without effect in this in vitro model. These results suggest that antidepressant-like activity of sigma receptor agonists is independent of corticosterone-induced gene transcription. Therefore, the attenuation of GR function induced by sigma receptor antagonists remains ambiguous and requires further study.
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PMID:Effects of selective sigma receptor ligands on glucocorticoid receptor-mediated gene transcription in LMCAT cells. 1921 81


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