scholarly journals Interactions of Estrogen- and Thyroid Hormone Receptors on a Progesterone Receptor Estrogen Response Element (ERE) Sequence: a Comparison with the Vitellogenin A2 Consensus ERE

1997 ◽  
Vol 11 (11) ◽  
pp. 1581-1592 ◽  
Author(s):  
Roderick E. M. Scott ◽  
X. Sharon Wu-Peng ◽  
Paul M. Yen ◽  
William W. Chin ◽  
Donald W. Pfaff
Keyword(s):  
Thyroid Hormone ◽  
Dna Binding ◽  
Reproductive Behavior ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Estrogen Response Element ◽  
Hormone Response ◽  
Response Element ◽  
Estrogen Response

Abstract The identification of hormone response elements in the promoter regions of hormonally regulated genes has revealed a striking similarity between the half-site of the estrogen-response element (ERE) and a consensus sequence constituting the thyroid hormone-response element. Because of the potential for thyroid hormone (T3) to affect estrogen (E)- and progesterone-dependent female reproductive behavior via EREs, we have begun to investigate the activity of an ERE identified in the progesterone receptor (PR) proximal promoter and its interactions with the estrogen receptor (ER) and thyroid hormone receptors (TR). In addition, we have compared ER and TR interactions on the PR ERE construct with that of the vitellogenin A2 (vit A2) consensus ERE. Electrophoretic mobility shift assays demonstrated that TR binds to the PR ERE as well as to the consensus ERE sequence in vitro. Further, these two EREs were differentially regulated by T3 in the presence of TR. T3 in the presence of TRα increased transcription from a PR ERE construct ∼5-fold and had no inhibitory effect on E induction. Similarly, T3 also activated a β-galactosidase reporter construct containing PR promoter sequences spanning −1400 to +700. In addition, the TR isoforms β1 and β2 also stimulated transcription from the PR ERE construct by 5- to 6-fold. A TRα mutant lacking the ability to bind AGGTCA sequences in vitro failed to activate transcription from the PR ERE construct, demonstrating dependence on DNA binding. In contrast to its actions on the PR ERE construct, TRα did not activate transcription from the vit A2 consensus ERE but rather attenuated E-mediated transcriptional activation. Attenuation from the vit A2 consensus ERE is not necessarily dependent on DNA binding as the TRα DNA binding mutant was still able to inhibit E-dependent transactivation. In contrast to TRα, the isoforms TRβ1 and TRβ2 failed to inhibit E-induced activation from the vit A2 consensus ERE. These results demonstrate that the PR ERE construct differs from the vit A2 consensus ERE in its ability to respond to TRs and that divergent pathways exist for activation and inhibition by TR. Since ERs, PRs, and TRs are all present in hypothalamic neurons, these findings may be significant for endocrine integration, which is important for reproductive behavior.

scholarly journals Thyroid hormone alters in vitro DNA binding of monomers and dimers of thyroid hormone receptors.

1992 ◽  
Vol 6 (7) ◽  
pp. 1142-1152
Author(s):  
R C Ribeiro ◽  
P J Kushner ◽  
J W Apriletti ◽  
B L West ◽  
J D Baxter
Keyword(s):  
Thyroid Hormone ◽  
Dna Binding ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptors

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.

scholarly journals Binding of Estrogen Receptor β to Estrogen Response Element in Situ Is Independent of Estradiol and Impaired by Its Amino Terminus

2005 ◽  
Vol 19 (11) ◽  
pp. 2696-2712 ◽  
Author(s):  
Jing Huang ◽  
Xiaodong Li ◽  
Casey A. Maguire ◽  
Russell Hilf ◽  
Robert A. Bambara ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Activation Function ◽  
Amino Terminus ◽  
Estrogen Response Element ◽  
Response Element ◽  
Estrogen Response ◽  
17Β Estradiol ◽  
Additional Explanation

Abstract The functions of 17β-estradiol (E2) are mediated by estrogen receptor (ER) α and β. ERs display similar DNA- and ligand-binding properties in vitro. However, ERβ shows lower transcriptional activity than ERα from the estrogen response element (ERE)-dependent signaling. We predicted that distinct amino termini contribute to differences in transcription efficacies of ERs by affecting in situ ER-ERE interactions. We used chromatin immunoprecipitation and a novel in situ ERE competition assay, which is based on the ability of ER to compete for ERE binding with a designer activator that constitutively induces transcription from an ERE-driven reporter construct. Interference of activator-mediated transcription by unliganded or liganded ERs was taken as an indication of ER-ERE interaction. Results revealed that ERs interacted with ERE similarly in the absence of E2. However, E2 enhanced the ERE binding of ERα but not that of ERβ. The removal of the amino terminus increased the ERβ-ERE interaction independent of E2. The ERβ amino terminus also prevented E2-mediated enhancement of the chimeric ERα-ERE interaction. Thus, the amino terminus of ERβ impairs the binding of ERβ to ERE. The abrogation of ligand-dependent activation function 2 of the amino-terminally truncated ERβ resulted in the manifestation of E2 effect on ERβ-ERE interaction. This implies that E2-mediated enhancement of ERβ-ERE interaction is masked by the activation function 2, whereas the intact amino terminus is a dominant region that decreases the binding of ERβ to ERE. Thus, ERβ-ERE interaction is independent of E2 and is impaired by its amino terminus. These findings provide an additional explanation for differences between ERα and ERβ functions that could differentially affect the physiology and pathophysiology of E2 signaling.

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