In vitro and in vivo interactions between nuclear receptors at estrogen response elements

1996 ◽  
Vol 58 (5-6) ◽  
pp. 507-515 ◽  
Author(s):  
A. Joyeux ◽  
P. Balaguer ◽  
D. Gagne ◽  
J.C. Nicolas
Keyword(s):  
Nuclear Receptors ◽  
Response Elements ◽  
Estrogen Response ◽  
Estrogen Response Elements

Peptide Binding Identifies an ERα Conformation That Generates Selective Activity in Multiple In Vitro Assays

2005 ◽  
Vol 10 (6) ◽  
pp. 590-598 ◽  
Author(s):  
Christopher J. Larson ◽  
Deborah L. Osburn ◽  
Katherine Schmitz ◽  
Leslie Giampa ◽  
Shau-Ming Mong ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Biological Effects ◽  
Peptide Binding ◽  
In Vitro Assays ◽  
Response Elements ◽  
Estrogen Response ◽  
Estrogen Response Elements ◽  
In Vivo Effects

Drugs such as tamoxifen, which act at the estrogen receptor (ER), have very different in vitro and in vivo effects from those of the native hormone. Previous research has established that different ligands induce distinct conformational changes in the ER, thus affecting the interactions of the receptor with cell-specific coactivating or corepressing proteins (cofactors) and estrogen response elements (EREs), thus potentially driving differing biological effects. Affinity-selected peptides have been used to probe the conformational changes that occur within the ER upon binding various ligands. In this study, the authors characterize the ability of several peptides to be recruited to liganded ER under cellular conditions. Approximating ER conformation via recruitment of this peptide to the ER is concluded to be a better predictor of the agonist nature of an ER ligand under these different cellular contexts than is a canonical cotransfection transactivation assay.

scholarly journals Utilization of DR1 as true RARE in regulating the Ssm, a novel retinoic acid-target gene in the mouse testis

2007 ◽  
Vol 192 (3) ◽  
pp. 539-551 ◽  
Author(s):  
Kyuyong Han ◽  
Haengseok Song ◽  
Irene Moon ◽  
Robert Augustin ◽  
Kelle Moley ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Promoter Region ◽  
Target Gene ◽  
Mouse Testis ◽  
Specific Marker ◽  
Specific Response ◽  
Response Elements

Various nuclear receptors form dimers to activate target genes via specific response elements located within promoters or enhancers. Retinoid X receptor (RXR) serves as a dimerization partner for many nuclear receptors including retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPAR). Dimers show differential preference towards directly repeated response elements with 1–5 nucleotide spacing, and direct repeat 1 (DR1) is a promiscuous element which recruits RAR/RXR, RXR/RXR, and PPAR/RXR in vitro. In the present investigation, we report identification of a novel RAR/RXR target gene which is regulated by DR1s in the promoter region. This gene, namely spermatocyte-specific marker (Ssm), recruits all the three combinations of nuclear receptors in vitro, but in vivo regulation is observed by trans-retinoic acid-activated RAR/RXR dimer. Indeed, chromatin immunoprecipitation experiment demonstrates binding of RARβ and RXRα in the promoter region of the Ssm. Interestingly, expression of Ssm is almost exclusively observed in spermatocytes in the adult mouse testis, where RA signaling is known to regulate developmental program of male germ cells. The results show that Ssm is a RAR/RXR target gene uniquely using DR1 and exhibits stage-specific expression in the mouse testis with potential function in later stages of spermatogenesis. This finding exemplifies usage of DR1s as retinoic acid response element (RARE) under a specific in vivo context.

scholarly journals Two functional estrogen response elements are located upstream of the major chicken vitellogenin gene.

1988 ◽  
Vol 8 (3) ◽  
pp. 1123-1131 ◽  
Author(s):  
J B Burch ◽  
M I Evans ◽  
T M Friedman ◽  
P J O'Malley
Keyword(s):  
Essential Feature ◽  
Coding Region ◽  
Transient Expression Assay ◽  
Specific Expression ◽  
Response Elements ◽  
Estrogen Response ◽  
Pair Sequence ◽  
Estrogen Response Elements ◽  
Vitellogenin Gene ◽  
Simplex Virus

We used a transient-expression assay to identify two estrogen response elements (EREs) associated with the major chicken vitellogenin gene (VTGII). Each element was characterized by its ability to confer estrogen responsiveness when cloned in either orientation next to a chimeric reporter gene consisting of the herpes simplex virus thymidine kinase promoter and the chloramphenicol acetyl transferase-coding region. Deletion analyses indicated that sequences necessary for the distal ERE resided within the region from -626 to -613 (nucleotide positions relative to the VTGII start site) whereas those necessary for the proximal ERE were within the region from -358 to -335. These distal and proximal elements contain, respectively, a perfect copy and an imperfect copy of the 13-base-pair sequence that is an essential feature of the EREs associated with two frog vitellogenin genes. These chicken VTGII EREs mapped near regions that were restructured at the chromatin level when the endogenous VTGII gene was expressed in the liver in response to estradiol. These data suggest a model for the tissue-specific expression of this estrogen-responsive gene.

scholarly journals Activating Signal Cointegrator 2 Belongs to a Novel Steady-State Complex That Contains a Subset of Trithorax Group Proteins

2003 ◽  
Vol 23 (1) ◽  
pp. 140-149 ◽  
Author(s):  
Young-Hwa Goo ◽  
Young Chang Sohn ◽  
Dae-Hwan Kim ◽  
Seung-Whan Kim ◽  
Min-Jung Kang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Steady State ◽  
Nuclear Receptors ◽  
Transcriptional Activation ◽  
Retinoic Acid Receptor ◽  
Dependent Manner ◽  
Trithorax Group ◽  
Trithorax Group Proteins

ABSTRACT Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. These include activating signal cointegrator 2 (ASC-2), a recently isolated transcriptional coactivator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors and numerous other transcription factors. In this report, we show that ASC-2 belongs to a steady-state complex of approximately 2 MDa (ASC-2 complex [ASCOM]) in HeLa nuclei. ASCOM contains retinoblastoma-binding protein RBQ-3, α/β-tubulins, and trithorax group proteins ALR-1, ALR-2, HALR, and ASH2. In particular, ALR-1/2 and HALR contain a highly conserved 130- to 140-amino-acid motif termed the SET domain, which was recently implicated in histone H3 lysine-specific methylation activities. Indeed, recombinant ALR-1, HALR, and immunopurified ASCOM exhibit very weak but specific H3-lysine 4 methylation activities in vitro, and transactivation by retinoic acid receptor appears to involve ligand-dependent recruitment of ASCOM and subsequent transient H3-lysine 4 methylation of the promoter region in vivo. Thus, ASCOM may represent a distinct coactivator complex of nuclear receptors. Further characterization of ASCOM will lead to a better understanding of how nuclear receptors and other transcription factors mediate transcriptional activation.

scholarly journals Liver X Receptor Nuclear Receptors Are Transcriptional Regulators of Dendritic Cell Chemotaxis

2018 ◽  
Vol 38 (10) ◽  
Author(s):  
Susana Beceiro ◽  
Attila Pap ◽  
Zsolt Czimmerer ◽  
Tamer Sallam ◽  
Jose A. Guillén ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Low Density Lipoprotein ◽  
Myeloid Cells ◽  
Density Lipoprotein ◽  
Loss Of Function ◽  
Transcriptional Responses ◽  
Cd38 Expression ◽  
The Impact

ABSTRACTThe liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DCs), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migrationin vitroandin vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished the LXR-dependent induction of DC chemotaxis. Using the low-density lipoprotein receptor-deficient (LDLR−/−) LDLR−/−mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for the efficient emigration of DCs in response to chemotactic signals during inflammation.

Sign in / Sign up

Export Citation Format

Share Document