Transcriptional Activities of the Orphan Nuclear Receptor ERRα (Estrogen Receptor-Related Receptor-α)

1999 ◽  
Vol 13 (5) ◽  
pp. 764-773 ◽  
Author(s):  
Jean-Marc Vanacker ◽  
Edith Bonnelye ◽  
Sandrine Chopin-Delannoy ◽  
Cateline Delmarre ◽  
Vincent Cavaillès ◽  
...  

Abstract Estrogen receptor-related receptor α (ERRα) is an orphan nuclear receptor closely related to the estrogen receptor (ER), whose expression covers various stages of embryonic development and persists in certain adult tissues. We show that ERRα binds as a homodimer on a specific target sequence, the SFRE (SF-1 response element), already known to respond to the orphan nuclear receptor SF-1. Target sequences that are related to the SFRE and that discriminate between ERRα and SF-1 were identified. We have also analyzed the transcriptional properties of the ERRα originating from various species. All ERRα orthologs act as potent transactivators through the consensus SFRE. ERRα activity depends on the putative AF2AD domain, as well as on a serum compound that is withdrawn by charcoal treatment, suggesting the existence of a critical regulating factor brought by serum.

2004 ◽  
Vol 18 (2) ◽  
pp. 312-325 ◽  
Author(s):  
Sabyasachi Sanyal ◽  
Jason Matthews ◽  
Didier Bouton ◽  
Han-Jong Kim ◽  
Hueng-Sik Choi ◽  
...  

2005 ◽  
Vol 186 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Sinead N Kelly ◽  
T Joseph McKenna ◽  
Leonie S Young

The capacity of the adrenal to produce steroids is controlled in part through the transcriptional regulation of steroid enzymes. The orphan nuclear receptor steroidogenic factor 1 (SF-1) is central to the transcriptional regulation of all steroid hydroxylase enzymes, whereas nur77 can preferentially regulate steroid enzyme genes relevant to cortisol production. We hypothesised that, in the presence of secretagogues, SF-1 and nur77 may differentially interact with coregulatory proteins in the human adrenal cortex. Both coregulatory proteins, steroid receptor coactivator (SRC-1) and silencing mediator for retinoid and thyroid hormones (SMRT), were found to be expressed in the zona fasciculata and reticularis in the human adrenal cortex, but were largely absent from the zona glomerulosa. Both coregulatory proteins were colocalised with SF-1 and nur77. In the H295R adrenal tumour cell line, SF-1 and nur77 transcripts were increased in cells in the presence of forskolin, whereas nur77 mRNA was also induced with angiotensin II (AII). The coactivator SRC-1 mRNA was increased in the presence of both forskolin and AII. Forskolin induced recruitment of SRC-1 to the SF-1 response element and induced SRC-1–SF-1 interactions, whereas AII increased recruitment of SRC-1 to the nur77 response element and induced SRC-1–nur77 interactions. The corepressor SMRT interacted with SF-1 in the presence of AII and with nur77 in cells treated with forskolin. Orphan nuclear receptor–coregulatory protein interactions may have consequences for the regulation of key steroidogenic enzymes in the human adrenal cortex.


2005 ◽  
Vol 79 (5) ◽  
pp. 2859-2868 ◽  
Author(s):  
Myrna M. Miller ◽  
Keith W. Jarosinski ◽  
Karel A. Schat

ABSTRACT Chicken anemia virus (CAV) is a small circular single-stranded DNA virus with a single promoter-enhancer region containing four consensus cyclic AMP response element sequences (AGCTCA), which are similar to the estrogen response element (ERE) consensus half-sites (A)GGTCA. These sequences are arranged as direct repeats, an arrangement that can be recognized by members of the nuclear receptor superfamily. Transient-transfection assays which use a short CAV promoter construct that ended at the transcription start site and drive expression of enhanced green fluorescent protein (EGFP) showed high basal activity in DF-1, LMH, LMH/2A, and primary theca and granulosa cells. The estrogen receptor-enhanced cell line, LMH/2A, had significantly greater expression than LMH cells, and this expression was significantly increased with estrogen treatment. A long promoter construct which included GGTCA-like sequences downstream of the first CAV protein translation start site was found to have significantly less EGFP expression in DF-1 cells than the short promoter, which was largely due to decreased RNA transcription. DNA-protein binding assays indicated that proteins recognizing a consensus ERE palindrome also bind GGTCA-like sequences in the CAV promoter. Estrogen receptor and other members of the nuclear receptor superfamily may provide a mechanism to regulate CAV activity in situations of low virus copy number.


2004 ◽  
Vol 33 (1) ◽  
pp. 87-97 ◽  
Author(s):  
B Horard ◽  
B Rayet ◽  
G Triqueneaux ◽  
V Laudet ◽  
F Delaunay ◽  
...  

Circadian gene expression has been demonstrated in many tissues and involves both positive and negative regulatory loops. The potential interferences of circadian rhythmicity with other well-known biologic rhythms, such as the ovarian cycle, at least in part controlled by estrogens, has not been questioned. The estrogen receptor-related receptor (ERR)alpha is an orphan nuclear receptor that is widely expressed in estrogen-responsive tissues such as liver, uterus and bone. In addition, expression of the ERRalpha gene has been proposed to be transcriptionally controlled by estrogens in the uterus. Here we show that the expression of ERRalpha displays a circadian rhythmicity in liver, bone and uterus. This is in contrast to other uterine estrogen-regulated genes. Analysis of clock/clock mutant mice shows that ERRalpha is an output gene of the circadian clock oscillator. The expression of clock-control genes, such as Bmal1 and Rev-erbalpha, also displays diurnal oscillations in the uterus, but not in bone. In this tissue, however, Per2 displayed a rhythmic expression, altogether suggesting unconventional loops in the regulation of circadian rhythm in bone.


2004 ◽  
Vol 33 (2) ◽  
pp. 493-509 ◽  
Author(s):  
B Horard ◽  
A Castet ◽  
P-L Bardet ◽  
V Laudet ◽  
V Cavailles ◽  
...  

The estrogen-receptor-related (ERR) receptors are orphan members of the nuclear receptor superfamily that bind to their specific DNA target sites as homodimers. However, it has not been shown whether this mode of binding is required for the transcriptional activation they drive. We here show that heterodimerization can also occur between these receptors. Furthermore, we demonstrate that the unique amphioxus ortholog of ERR genes (AmphiERR) is expressed as two isoforms differing by an in-frame insertion. While the short isoform behaves like its mammalian counterparts, the long isoform (AmphiERR(L)) displays divergent transcriptional properties according to the target site to which it binds. Indeed, AmphiERR(L) binds as a monomer but does not activate transcription through the SF1 response element (SFRE). On the contrary, this isoform binds as a homodimer and activates transcription through the classical estrogen-response element. Our results strongly suggest that dimerization is required for transactivation exerted by the ERR receptors.


2009 ◽  
Vol 284 (21) ◽  
pp. 14211-14218 ◽  
Author(s):  
Byung-Chul Jeong ◽  
Yong-Soo Lee ◽  
Yun-Yong Park ◽  
In-Ho Bae ◽  
Don-Kyu Kim ◽  
...  

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