Association of DNA-bound progesterone receptors

Théveny, B; Bailly, Alain; Rauch, Claudine; Rauch, Michel; Delain, Etienne; Milgröm, Edwin

doi:10.1038/329079a0

Cited by 110 publications

(37 citation statements)

References 20 publications

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“…Nucleosome phasing (32) might therefore bring the GREs close enough to each other to allow biological activity for the GREa and GREd by providing multiple contacts with the RNA polymerase II initiation complex. Similar protein-protein interactions mediated by the progesterone receptor bound to distal hormone responsive elements have been reported for the uteroglobin gene (33). Interaction between distal regulatory loci and the basic transcription complex requires looping which depends on protein/ protein interactions between transcription factors bound, respectively, to the enhancer and to the proximal promoter (34).…”

Section: Discussionmentioning

confidence: 84%

Identification of a Multihormone Responsive Enhancer Far Upstream from the Human Tissue-type Plasminogen Activator Gene

Bulens

Merchiers²,

Ibañez–Tallon³

et al. 1997

Journal of Biological Chemistry

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A 2.4-kilobase (kb) DNA fragment, located 7.1 kb upstream from the human tissue-type plasminogen activator (t-PA) gene (t-PA2.4), acts as an enhancer which is activated by glucocorticoids, progesterone, androgens, and mineralocorticoids. Transient expression of t-PAchloramphenicol acetyltransferase reporter constructs in HT1080 human fibrosarcoma cells identified a glucocorticoid responsive unit with four functional binding sites for the glucocorticoid receptor, located between bp ؊7,501 and ؊7,974. The region from bp ؊7,145 to ؊9,578 (t-PA2.4) was found to confer a cooperative induction by dexamethasone and all-trans-retinoic acid (RA) to its homologous and a heterologous promoter, irrespective of its orientation. The minimal enhancer, defined by progressive deletion analysis, comprised the region from ؊7.1 to ؊8.0 kb (t-PA0.9) and encompassed the glucocorticoid responsive unit and the previously identified RA-responsive element located at ؊7. Vascular patency is the result of a dynamic equilibrium between blood coagulation and fibrinolysis. Injury of the vessel wall can initiate the blood clotting cascade resulting in the formation of a hemostatic clot. To counterbalance fibrin deposition, blood contains the fibrinolytic system, one main function of which is to dissolve blood clots in the circulation. It is composed of the inactive precursor plasminogen, which can be converted into the proteolytic enzyme plasmin by the plasminogen activators (PAs) 1 tissue-type and urokinase-type PA (t-PA and u-PA, respectively) leading to the degradation of fibrin. Fibrinolytic activity can be inhibited both at the level of the PAs and plasmin by PA inhibitors (PAI-1 and -2) and ␣ 2 -antiplasmin, respectively (for a review, see ref. 1). Phenotypic analysis of mice deficient for either t-PA, u-PA, or both suggested that t-PA and u-PA were complementary, not only in the prevention of uncontrolled fibrin deposition in vivo but also in distinct processes which require local extracellular proteolytic activity, such as wound healing and gonadotropin-induced ovulation, as reviewed elsewhere (2).Dexamethasone, a synthetic glucocorticoid, and androgens increase t-PA synthesis in vitro (3-5) and in vivo (6, 7). The level of t-PA expression in breast carcinoma cells correlates with the endogenous level of progesterone receptor (8), and progesterone induces t-PA-related antigen secretion in primary human endometrial cells (9). Vitamin A, retinoic acid (RA), and some of its (synthetic) analogues induce t-PA-related antigen secretion by human umbilical vein endothelial cells in vitro (10 -12) and in the plasma as well as in specific tissues of vitamin A-deficient rats in vivo (11,13,14), suggesting that circulating RA might regulate t-PA expression in the vessel wall. The induction of t-PA expression by glucocorticoids and RA can be reproduced in HT1080 human fibrosarcoma cells, and interestingly, both agents induce t-PA mRNA steady state levels and t-PA-related antigen secretion in a cooperative manner.2 Both steroid hormones and RA are t...

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Section: Discussionmentioning

confidence: 84%

Identification of a Multihormone Responsive Enhancer Far Upstream from the Human Tissue-type Plasminogen Activator Gene

Bulens

Merchiers²,

Ibañez–Tallon³

et al. 1997

Journal of Biological Chemistry

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“…This suggests that the effect of the spacer is due to the disruption of the relative arrangement of distal versus proximal regulatory elements, rather than to the presence of sequences contained in the inserted DNA. That physical interactions between receptors can occur was shown in an electron microscopy study (50) in which progesterone receptors appeared associated in pairs on the MMTV HRE. Using the same constructs, we observed a similar requirement for spacing of the elements in the glucocorticoid response in Ltk-cells (6).…”

Section: Discussionmentioning

confidence: 98%

Mutations in the hormone regulatory element of mouse mammary tumor virus differentially affect the response to progestins, androgens, and glucocorticoids.

Gowland¹,

Buetti²

1989

Mol. Cell. Biol.

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Transcription of the mouse mammary tumor virus DNA is known to be induced by several steroid hormones. Using chimeric MMTV plasmids containing mutations within the hormone regulatory element, we have previously studied the regions required for the glucocorticoid response in mouse fibroblasts. Here we report the characterization of elements essential for the stimulation by progestins and androgens as compared with glucocorticoids. The same set of mutant plasmids was transfected into the human mammary tumor cell line T47D, and the specific transcripts were analyzed by an Si nuclease protection assay. Androgen-mediated stimulation, although weak, showed an extended sensitivity to mutations, with a slight preference for the proximal region. The results with progestin suggest that sequences within all the described sites protected by the receptor in vitro are required and that the promoter-proximal region (-128 to -78 from the RNA start site) is more important than the distal one (-190 to -160). Moreover, a binding site for nuclear factor I was not required for the progestin response, whereas it was required for glucocorticoids. Thus, the various steroid receptors play a role in the differential regulation of mouse mammary tumor virus transcription by recognizing distinct sequence differences in the hormone regulatory element and interacting with different factors bound to the promoter.The mouse mammary tumor virus (MMTV) has been successfully used as a model for studying the control of gene expression by steroid hormones (reviewed in references 41 and 54). In particular, glucocorticoids have been shown to stimulate MMTV transcription in infected cells (42,55) through the action of the glucocorticoid receptor. Mainly because of the widespread occurrence of this receptor in cultured cell lines, the DNA sequences required for glucocorticoid regulation have been investigated in more detail by using cells transfected with chimeric DNA molecules (25,28) and have subsequently been mapped to the 200 base pairs (bp) upstream of the MMTV RNA start site in the viral long terminal repeat (LTR) (4,26,31). Using a series of mutant plasmids containing clustered point mutations, small deletions, or additions, we demonstrated that maximal stimulation by glucocorticoids requires the cooperative action of multiple, distinct sequence elements (5, 27). The strongest, distal element maps at -181 to -172, inside an area that binds the purified glucocorticoid receptor (39, 44). Further elements map around -120, in one of the three proximal receptor-binding sites (43), and in the symmetric sequence around -70 recognized by nuclear factor I (NF-I [35,38] described previously (5, 27). The results provide evidence that in the natural context of the MMTV promoter, the proximal upstream region is more important than the distal one for the progestin and possibly the androgen responses and that the NF-I binding site is not required for the progestin response, in contrast to the situation observed with glucocorticoids. It is suggested that subtle ...

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“…A number of findings favor such speculations. Firstly, when bound to DNA, steroid hormone receptors still have the ability to interact with each other, as revealed by electron microscopic studies (31). Secondly, different progesterone receptor amino-terminal mutants have been shown to interact differently with the estrogen receptor in the regulation of transcription at the chicken ovalbumin promoter (32).…”

Section: Discussionmentioning

confidence: 99%

Estrogen and progesterone receptor-binding sites on the chicken vitellogenin II gene: synergism of steroid hormone action.

Cato¹,

Heitlinger²,

Ponta³

et al. 1988

Mol. Cell. Biol.

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The chicken vitellogenin II gene is transcriptionally activated by estrogens. In transient transfection experiments in human T47D cells that contain receptors for various steroids, we showed estradiol, progestin, and androgen responses of a chimeric chicken vitellogenin II construct. This construct consists of DNA sequences from -626 to -590 upstream of the start of transcription of the chicken viteliogenin gene linked to the herpes simplex virus thymidine kinase promoter driving the transcription of the bacterial chloramphenicol acetyltransferase gene. Treatment of the transfected T47D cells with a combination of estradiol and the progestin R5020 led to a superinduction of chloramphenicol acetyltransferase activity, showing a synergistic action of these two steroids. This synergism was not observed upon treatment of the transfected cells with estradiol and the androgen dihydrotestosterone. Using point mutations in the vitellogenin gene fragment, we showed in functional and in in vitro DNase I footprinting assays with a purified progesterone receptor that, for the synergistic action of estradiol and R5020 to occur, the progesterone receptor must be bound to the vitellogenin gene fragment. The progesterone receptor-binding site was localized at -610 to -590, close to the consensus sequence (-626 to -613) for estrogen receptor binding and function. We therefore demonstrate here that two different steroid hormones can be functionally synergistic through the interaction of their corresponding receptors with two different binding sites adjacent to one another.The regulation of gene expression by steroid hormones is thought to occur through the interaction of steroid hormone receptor complexes with discrete nucleotide sequences in the neighborhood of the promoters of inducible genes (for reviews, see references 2 and 35). Short perfect or imperfect palindromic sequences that mediate steroid hormone action have been identified near the promoters of a number of steroid hormone-regulated genes. For example, 13-base-pair (bp) palindromic elements that mediate the estrogen response have been identified near the promoters of the Xenopus and chicken vitellogenin genes (4,17,18,19,22). Similarly, 15-bp perfect or imperfect palindromes that encompass the hexanucleotide motif 5'-TGTT/CCT-3' have been shown to mediate glucocorticoid and progestin responses in a number of genes (5,6,29,30). The delimitation of these short nucleotide sequences was achieved through gene transfer studies with either in vitro mutagenesis of known hormone receptor-binding sites (6) or different chimeras containing synthetic oligonucleotides (13,17,30). In a number of hormone response elements, such as that in mouse mammary tumor virus DNA (3, 6), the tyrosine aminotransferase gene (13), and the Xenopus vitellogenin Bi and chicken vitellogenin II (VTG II) genes (4,16,22,27) sites function by cooperating with the binding sites for other transcriptional factors that lie in their immediate vicinity.In the VTG II gene, a gene whose transcription is known t...

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Association of DNA-bound progesterone receptors

Cited by 110 publications

References 20 publications

Identification of a Multihormone Responsive Enhancer Far Upstream from the Human Tissue-type Plasminogen Activator Gene

Identification of a Multihormone Responsive Enhancer Far Upstream from the Human Tissue-type Plasminogen Activator Gene

Mutations in the hormone regulatory element of mouse mammary tumor virus differentially affect the response to progestins, androgens, and glucocorticoids.

Estrogen and progesterone receptor-binding sites on the chicken vitellogenin II gene: synergism of steroid hormone action.

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