Estrogen receptor mutants which do not bind 17 beta-estradiol dimerize and bind to the estrogen response element in vivo

1995 ◽  
Vol 9 (4) ◽  
pp. 457-466 ◽  
Author(s):  
Y. Zhuang
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response

scholarly journals A Novel Estrogen Receptor α-Associated Protein Alters Receptor-Deoxyribonucleic Acid Interactions and Represses Receptor-Mediated Transcription

2004 ◽  
Vol 18 (11) ◽  
pp. 2649-2659 ◽  
Author(s):  
Margaret A. Loven ◽  
Roger E. Davis ◽  
Carol D. Curtis ◽  
Nemone Muster ◽  
John R. Yates ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Thyroid Hormone Receptor ◽  
Estrogen Receptor Α ◽  
Target Cells ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response ◽  
Mcf 7

Abstract Estrogen receptor α (ERα) serves as a ligand-activated transcription factor, turning on transcription of estrogen-responsive genes in target cells. Numerous regulatory proteins interact with the receptor to influence ERα-mediated transactivation. In this study, we have identified pp32, which interacts with the DNA binding domain of ERα when the receptor is free, but not when it is bound to an estrogen response element. Coimmunoprecipitation experiments demonstrate that endogenously expressed pp32 and ERα from MCF-7 breast cancer cells interact. Although pp32 substantially enhances the association of the receptor with estrogen response element-containing DNA, overexpression of pp32 in MCF-7 cells decreases transcription of an estrogen-responsive reporter plasmid. pp32 Represses p300-mediated acetylation of ERα and histones in vitro and inhibits acetylation of ERα in vivo. pp32 Also binds to other nuclear receptors and inhibits thyroid hormone receptor β-mediated transcription. Taken together, our studies provide evidence that pp32 plays a role in regulating transcription of estrogen-responsive genes by modulating acetylation of histones and ERα and also influences transcription of other hormone-responsive genes as well.

scholarly journals Estradiol and Tamoxifen Mediate Rescue of the Dominant-Negative Effects of Estrogen Response Element-Binding Protein in Vivo and in Vitro

Endocrinology ◽  
2008 ◽  
Vol 150 (5) ◽  
pp. 2429-2435 ◽  
Author(s):  
Hong Chen ◽  
Thomas L. Clemens ◽  
Martin Hewison ◽  
John S. Adams
Keyword(s):  
Estrogen Receptor ◽  
Transgenic Mice ◽  
Binding Protein ◽  
Fold Increase ◽  
Estrogen Response Element ◽  
Wild Type ◽  
Branch Number ◽  
Response Element ◽  
Estrogen Response

Biological responses to estrogens are dependent on the integrated actions of proteins, including the estrogen receptor (ER)-α, that regulate the transcription of estrogen response element (ERE)-containing target genes. We have identified a naturally occurring ERE antagonist, termed an ERE-binding protein (BP). To verify that ERE-BP can induce estradiol (E2) resistance in vivo, we generated transgenic mice that overexpress this protein in breast tissue. Female transgenic mice with high levels of ERE-BP were unable to lactate, and we hypothesized that this effect was dependent on the relative levels of ERE-BP and ERα ligand. To test this hypothesis, wild-type and ERE-BP-expressing female mice were implanted with capsules containing E2, the selective estrogen receptor modulator tamoxifen, or placebo. Histological analysis of nonlactating mammary glands showed a 4.5-fold increase in gland branch number and 3.7-fold increase in ducts in ERE-BP mice treated with E2 (7.5 mg, 21 d) compared with placebo-treated ERE-BP mice. Wild-type mice showed a 5.3-fold increase in branches and 1.4-fold increase in ducts under the same conditions. Similar results were obtained with tissue from lactating mice, in which tamoxifen also increased mammary gland branch number. Studies using ERE-BP-expressing MCF-7 breast cells showed that high doses of E2 (1000 nm) restored normal ERα-chromatin interaction in these cells, whereas tamoxifen was able to achieve this effect at a dose of 10 nm. These data highlight the importance of ERE-BP as an attenuator of normal ERα signaling in vivo and further suggest that ERE-BP is a novel target for modulation by selective estrogen receptor modulators.

scholarly journals Mouse Estrogen Receptor β Forms Estrogen Response Element-Binding Heterodimers with Estrogen Receptor α

1997 ◽  
Vol 11 (10) ◽  
pp. 1486-1496 ◽  
Author(s):  
Katarina Pettersson ◽  
Kaj Grandien ◽  
George G. J. M. Kuiper ◽  
Jan-Åke Gustafsson
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Β ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response

scholarly journals Aromatase: Contributions to Physiology and Disease in Women and Men

Physiology ◽  
2016 ◽  
Vol 31 (4) ◽  
pp. 258-269 ◽  
Author(s):  
Jennifer Blakemore ◽  
Fredrick Naftolin
Keyword(s):  
Human Physiology ◽  
Estrogen Receptor ◽  
Aromatase Inhibitors ◽  
Reproductive System ◽  
Short Review ◽  
Estrogen Response Element ◽  
Comprehensive Overview ◽  
Response Element ◽  
Estrogen Response ◽  
Health And Disease

Aromatase (estrogen synthetase; EC 1.14.14.1) catalyzes the demethylation of androgens' carbon 19, producing phenolic 18-carbon estrogens. Aromatase is most widely known for its roles in reproduction and reproductive system diseases, and as a target for inhibitor therapy in estrogen-sensitive diseases including cancer, endometriosis, and leiomyoma (141, 143). However, all tissues contain estrogen receptor-expressing cells, the majority of genes have a complete or partial estrogen response element that regulates their expression (61), and there are plentiful nonreceptor effects of estrogens (79); therefore, the effect of aromatase through the provision of estrogen is almost universal in terms of health and disease. This review will provide a brief but comprehensive overview of the enzyme, its role in steroidogenesis, the problems that arise with its functional mutations and mishaps, the roles in human physiology of aromatase and its product estrogens, its current clinical roles, and the effects of aromatase inhibitors. While much of the story is that of the consequences of the formation of its product estrogens, we also will address alternative enzymatic roles of aromatase as a demethylase or nonenzymatic actions of this versatile molecule. Although this short review is meant to be thorough, it is by no means exhaustive; rather, it is meant to reflect the cutting-edge, exciting properties and possibilities of this ancient enzyme and its products.

scholarly journals The High Mobility Group Protein 1 Enhances Binding of the Estrogen Receptor DNA Binding Domain to the Estrogen Response Element

1998 ◽  
Vol 12 (5) ◽  
pp. 664-674 ◽  
Author(s):  
Lorene E. Romine ◽  
Jennifer R. Wood ◽  
LuAnne A. Lamia ◽  
Paul Prendergast ◽  
Dean P. Edwards ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Dna Binding ◽  
High Mobility ◽  
High Mobility Group ◽  
Estrogen Response Element ◽  
Dna Binding Domain ◽  
High Mobility Group Protein ◽  
Response Element ◽  
Estrogen Response ◽  
Group Protein

Abstract We have examined the ability of the high-mobility group protein 1 (HMG1) to alter binding of the estrogen receptor DNA-binding domain (DBD) to the estrogen response element (ERE). HMG1 dramatically enhanced binding of purified, bacterially expressed DBD to the consensus vitellogenin A2 ERE in a dose-dependent manner. The ability of HMG1 to stabilize the DBD-ERE complex resulted in part from a decrease in the dissociation rate of the DBD from the ERE. Antibody supershift experiments demonstrated that HMG1 was also capable of forming a ternary complex with the ERE-bound DBD in the presence of HMG1-specific antibody. HMG1 did not substantially affect DBD-ERE contacts as assessed by methylation interference assays, nor did it alter the ability of the DBD to induce distortion in ERE-containing DNA fragments. Because HMG1 dramatically enhanced estrogen receptor DBD binding to the ERE, and the DBD is the most highly conserved region among the nuclear receptor superfamily members, HMG1 may function to enhance binding of other nuclear receptors to their respective response elements and act in concert with coactivator proteins to regulate expression of hormone-responsive genes.

Regulation of HOXA10 expression by phytoestrogens

2007 ◽  
Vol 292 (2) ◽  
pp. E435-E442 ◽  
Author(s):  
G. Eda Akbas ◽  
Xiaolan Fei ◽  
Hugh S. Taylor
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
In Utero ◽  
Estrogen Response Element ◽  
Mouse Uterus ◽  
Response Element ◽  
Estrogen Response ◽  
Uterine Anomalies ◽  
Mrna And Protein Expression ◽  
Adult Exposure

HOXA10 is necessary for normal development of the Müllerian duct, and continued adult expression in the uterus is necessary for female fertility. HOXA10 expression is altered by diethylstilbestrol, leading to uterine anomalies. Other endocrine disruptors may potentially lead to reproductive anomalies or dysfunction by altering HOXA10 expression. Here we investigated the effect of isoflavones on HOXA10 expression after in utero or adult exposure in the mouse. Genistein, but not diadzein, regulated HOXA10 mRNA and protein expression in the adult mouse uterus. In contrast, in utero genistein or diadzein exposure had no lasting effect on HOXA10 expression in the exposed offspring. Reporter gene expression driven by the HOXA10 estrogen response element was increased in a dose-responsive manner by genistein, but not daidzein. Neither estrogen receptor-α nor estrogen receptor-β binding to the HOXA10 estrogen response element was affected by genistein or daidzein. In utero exposure to isoflavones is unlikely to result in HOXA10-mediated developmental anomalies. Adult genistein exposure alters uterine HOXA10 expression, a potential mechanism by which this agent affects fertility.

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