Identification of an Essential cis-acting Element (TR2-PACE) in the 5' Promoter of Human TR2 Orphan Receptor Gene

Endocrine ◽  
2000 ◽  
Vol 12 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Din-Lii Lin ◽  
Chawnshang Chang
Keyword(s):  
Receptor Gene ◽  
Orphan Receptor ◽  
Cis Acting

Amplification and overexpression of oncogene Mdm2 and orphan receptor gene Nr1h4 in immortal PRKDC knockout cells

2004 ◽  
Vol 31 (2) ◽  
pp. 91-96 ◽  
Author(s):  
Rong Ai ◽  
Ana Sandoval ◽  
David J. Chen ◽  
Sandeep Burma ◽  
Paul Labhart
Keyword(s):  
Receptor Gene ◽  
Orphan Receptor

scholarly journals Transcriptional Regulation of Mouse μ Opioid Receptor Gene by PU.1

2004 ◽  
Vol 279 (19) ◽  
pp. 19764-19774 ◽  
Author(s):  
Cheol Kyu Hwang ◽  
Chun Sung Kim ◽  
Hack Sun Choi ◽  
Scott R. McKercher ◽  
Horace H. Loh
Keyword(s):  
Transcription Factors ◽  
Opioid Receptor ◽  
Trichostatin A ◽  
Receptor Gene ◽  
Hematopoietic Cells ◽  
Mobility Shift ◽  
Knock Out ◽  
Cis Acting ◽  
Μ Opioid Receptor ◽  
Mobility Shift Assay

We previously reported that the 34-bp cis-acting element of the mouse μ opioid receptor (MOR) gene represses transcription of the MOR gene from the distal promoter. Using a yeast one-hybrid screen to identify potential transcription factors of the MOR promoter, we have identified PU.1 as one of the candidate genes. PU.1 is a member of theetsfamily of transcription factors, expressed predominantly in hematopoietic cells and microglia of brain. PU.1 plays an essential role in the development of both lymphoid and myeloid lineages. Opioids exert neuromodulatory as well as immunomodulatory effects, which are transduced by MOR. Moreover, MOR-deficient mice exhibit increased proliferation of hematopoietic cells, suggesting a possible link between the opioid system and hematopoietic development. The PU.1 protein binds to the 34-bp element of the MOR gene in a sequence-specific manner confirmed by electrophoretic mobility shift assay and supershift assays. We have also determined endogenous PU.1 interactions with the 34-bp element of MOR promoter by chromatin immunoprecipitation assays. In co-transfection studies PU.1 represses MOR promoter reporter constructs through its PU.1 binding site. When the PU.1 gene is disrupted as in PU.1 knock-out mice and using small interfering RNA-based strategy in RAW264.7 cells, the transcription of the endogenous target MOR gene is increased significantly. This increase is probably mediated through modification of the chromatin structure, as suggested by the reversal of the PU.1-mediated repression of MOR promoter activity after trichostatin A treatment in neuroblastoma NMB cells. Our results suggest that PU.1 may be an important regulator of the MOR gene, particularly in brain and immune cells.

Suppression of HGF receptor gene expression by oxidative stress is mediated through the interplay between Sp1 and Egr-1

2003 ◽  
Vol 284 (6) ◽  
pp. F1216-F1225 ◽  
Author(s):  
Xianghong Zhang ◽  
Youhua Liu
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Collecting Duct ◽  
Receptor Gene ◽  
Ectopic Expression ◽  
Transcriptional Activator ◽  
Physical Interaction ◽  
Nucleotide Position ◽  
Renal Epithelial Cells ◽  
Cis Acting

Hepatocyte growth factor (HGF) receptor, the product of the c-metprotooncogene, is transcriptionally regulated by a wide variety of cytokines as well as extracellular environmental cues. In this report, we demonstrate that c-met expression was significantly suppressed by oxidative stress. Treatment of mouse renal inner medullary collecting duct epithelial cells with 0.5 mM H2O2inhibited c-met mRNA and protein expression, which was concomitant with induction of Egr-1 transcription factor. Ectopic expression of Egr-1 in renal epithelial cells markedly inhibited endogenous c-met expression in a dose-dependent fashion, suggesting a causative effect of Egr-1 in mediating c-met suppression. The cis-acting element responsible for H2O2-induced c-met inhibition was localized at nucleotide position −223 to −68 of c-met promoter, in which reside an imperfect Egr-1 and three Sp1-binding sites. Egr-1 markedly suppressed c-met promoter activity but did not directly bind to its cis-acting element in the c-met gene. Induction of Egr-1 by oxidative stress attenuated the binding of Sp1 to its cognate sites, but it did not affect Sp1 abundance in renal epithelial cells. Immunoprecipitation uncovered that Egr-1 physically interacted with Sp1 by forming the Sp1/Egr-1 complex, which presumably resulted in a decreased availability of unbound Sp1 as a transcriptional activator for the c-met gene. Thus it appears that inhibition of c-met expression by oxidative stress is mediated by the interplay between Sp1 and Egr-1 transcription factors. Our findings reveal a novel transcriptional regulatory mechanism by which Egr-1 sequesters Sp1 as a transcriptional activator of c-met via physical interaction.

Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor

1994 ◽  
Vol 14 (9) ◽  
pp. 5756-5765
Author(s):  
J Casanova ◽  
E Helmer ◽  
S Selmi-Ruby ◽  
J S Qi ◽  
M Au-Fliegner ◽  
...  
Keyword(s):  
Amino Acids ◽  
Retinoic Acid ◽  
Amino Acid ◽  
Thyroid Hormone ◽  
Ligand Binding ◽  
Receptor Gene ◽  
Binding Domain ◽  
Orphan Receptor ◽  
Cellular Factor ◽  
Receptor Inhibitor

The ligand-binding domains of thyroid hormone (L-triiodothyronine [T3]) receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), and 9-cis RA receptors (RARs and RXRs) contain a series of heptad motifs thought to be important for dimeric interactions. Using a chimera containing amino acids 120 to 392 of chicken T3R alpha (cT3R alpha) positioned between the DNA-binding domain of the yeast GAL4 protein and the potent 90-amino-acid transactivating domain of the herpes simplex virus VP16 protein (GAL4-T3R-VP16), we provide functional evidence that binding of ligand releases T3Rs and RARs from an inhibitory cellular factor. GAL4-T3R-VP16 does not bind T3 and does not activate transcription from a GAL4 reporter when expressed alone but is able to activate transcription when coexpressed with unliganded T3R or RAR. This activation is reversed by T3 or RA, suggesting that these receptors compete with GAL4-T3R-VP16 for a cellular inhibitor and that ligand reverses this effect by dissociating T3R or RAR from the inhibitor. A chimera containing the entire ligand-binding domain of cT3R alpha (amino acids 120 to 408) linked to VP16 [GAL4-T3R(408)-VP16] is activated by unliganded receptor as well as by T3. In contrast, GAL4-T3R containing the amino acid 120 to 408 ligand-binding region without the VP16 domain is activated only by T3. The highly conserved ninth heptad, which is involved in heterodimerization, appears to participate in the receptor-inhibitor interaction, suggesting that the inhibitor is a related member of the receptor gene family. In striking contrast to T3R and RAR, RXR activates GAL4-T3R-VP16 only with its ligand, 9-cis RA, but unliganded RXR does not appear to be the inhibitor suggested by these studies. Further evidence that an orphan receptor may be the inhibitor comes from our finding that COUP-TF inhibits activation of GAL4-T3R-VP16 by unliganded T3R and the activation of GAL4-T3R by T3. These and other results suggest that an inhibitory factor suppresses transactivation by the T3Rs and RARs while these receptors are bound to DNA and that ligands act, in part, by inactivating or promoting dissociation of a receptor-inhibitor complex.

scholarly journals The Glucocorticoid Receptor Represses the Positive Autoregulation of the Trout Estrogen Receptor Gene by Preventing the Enhancer Effect of a C/EBPβ-Like Protein

Endocrinology ◽  
2002 ◽  
Vol 143 (8) ◽  
pp. 2961-2974 ◽  
Author(s):  
Christèle Lethimonier ◽  
Gilles Flouriot ◽  
Olivier Kah ◽  
Bernadette Ducouret
Keyword(s):  
Glucocorticoid Receptor ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Receptor Gene ◽  
Inhibitory Effect ◽  
Proximal Region ◽  
Orphan Receptor ◽  
Protein Protein Interactions ◽  
Negative Effects ◽  
Er Positive

Abstract Stress and cortisol are known to have negative effects on vitellogenesis in oviparous species. This provides a physiological context in which to explore in more detail the molecular mechanisms involved in transcriptional interferences between two steroids receptors, the estradiol receptor (ER) and the glucocorticoid receptor (GR). We have previously shown that the cortisol inhibitory effect on rainbow trout (rt) vitellogenesis is the result of a repression of the estradiol-induced ER-positive autoregulation by activated GR. In the present study, we demonstrate that the GR repression involves a proximal region of the rtER promoter that is unable to bind GR. This inhibition is counteracted in part by the orphan receptor COUP-TF1 that has been previously shown to cooperate with ERs on the same promoter. A detailed analysis allowed us to identify a C/EBPβ-like protein that is implicated in both the maximal stimulatory effect of estradiol and the GR repression. Indeed, GR, through its DNA-binding domain, suppresses the binding of C/EBPβ on the rtER promoter by protein-protein interactions and thereby prevents the enhancer effect of this transcription factor.

scholarly journals Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor.

1994 ◽  
Vol 14 (9) ◽  
pp. 5756-5765 ◽  
Author(s):  
J Casanova ◽  
E Helmer ◽  
S Selmi-Ruby ◽  
J S Qi ◽  
M Au-Fliegner ◽  
...  
Keyword(s):  
Amino Acids ◽  
Retinoic Acid ◽  
Amino Acid ◽  
Thyroid Hormone ◽  
Ligand Binding ◽  
Receptor Gene ◽  
Binding Domain ◽  
Orphan Receptor ◽  
Cellular Factor ◽  
Receptor Inhibitor

The ligand-binding domains of thyroid hormone (L-triiodothyronine [T3]) receptors (T3Rs), all-trans retinoic acid (RA) receptors (RARs), and 9-cis RA receptors (RARs and RXRs) contain a series of heptad motifs thought to be important for dimeric interactions. Using a chimera containing amino acids 120 to 392 of chicken T3R alpha (cT3R alpha) positioned between the DNA-binding domain of the yeast GAL4 protein and the potent 90-amino-acid transactivating domain of the herpes simplex virus VP16 protein (GAL4-T3R-VP16), we provide functional evidence that binding of ligand releases T3Rs and RARs from an inhibitory cellular factor. GAL4-T3R-VP16 does not bind T3 and does not activate transcription from a GAL4 reporter when expressed alone but is able to activate transcription when coexpressed with unliganded T3R or RAR. This activation is reversed by T3 or RA, suggesting that these receptors compete with GAL4-T3R-VP16 for a cellular inhibitor and that ligand reverses this effect by dissociating T3R or RAR from the inhibitor. A chimera containing the entire ligand-binding domain of cT3R alpha (amino acids 120 to 408) linked to VP16 [GAL4-T3R(408)-VP16] is activated by unliganded receptor as well as by T3. In contrast, GAL4-T3R containing the amino acid 120 to 408 ligand-binding region without the VP16 domain is activated only by T3. The highly conserved ninth heptad, which is involved in heterodimerization, appears to participate in the receptor-inhibitor interaction, suggesting that the inhibitor is a related member of the receptor gene family. In striking contrast to T3R and RAR, RXR activates GAL4-T3R-VP16 only with its ligand, 9-cis RA, but unliganded RXR does not appear to be the inhibitor suggested by these studies. Further evidence that an orphan receptor may be the inhibitor comes from our finding that COUP-TF inhibits activation of GAL4-T3R-VP16 by unliganded T3R and the activation of GAL4-T3R by T3. These and other results suggest that an inhibitory factor suppresses transactivation by the T3Rs and RARs while these receptors are bound to DNA and that ligands act, in part, by inactivating or promoting dissociation of a receptor-inhibitor complex.

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