Requirements for transcriptional regulation by the orphan nuclear receptor ERRgamma

2004 ◽  
Vol 219 (1-2) ◽  
pp. 151-160 ◽  
Author(s):  
Johanna Huppunen ◽  
Gerd Wohlfahrt ◽  
Piia Aarnisalo
Keyword(s):  
Transcriptional Regulation ◽  
Nuclear Receptor ◽  
Orphan Nuclear Receptor

scholarly journals Coregulatory protein–orphan nuclear receptor interactions in the human adrenal cortex

2005 ◽  
Vol 186 (1) ◽  
pp. 33-42 ◽  
Author(s):  
Sinead N Kelly ◽  
T Joseph McKenna ◽  
Leonie S Young
Keyword(s):  
Transcriptional Regulation ◽  
Adrenal Cortex ◽  
Nuclear Receptor ◽  
Tumour Cell Line ◽  
Zona Fasciculata ◽  
Orphan Nuclear Receptor ◽  
Response Element ◽  
Coregulatory Proteins ◽  
Coregulatory Protein ◽  
In Cells

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.

scholarly journals Orphan Nuclear Receptor ERRγ Is a Novel Transcriptional Regulator of IL-6 Mediated Hepatic BMP6 Gene Expression in Mice

2020 ◽  
Vol 21 (19) ◽  
pp. 7148
Author(s):  
Kamalakannan Radhakrishnan ◽  
Yong-Hoon Kim ◽  
Yoon Seok Jung ◽  
Jina Kim ◽  
Don-Kyu Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Molecular Mechanism ◽  
Nuclear Receptor ◽  
Iron Homeostasis ◽  
Luciferase Reporter ◽  
Orphan Nuclear Receptor ◽  
Knock Out

Bone morphogenetic protein 6 (BMP6) is a multifunctional growth factor involved in organ development and homeostasis. BMP6 controls expression of the liver hormone, hepcidin, and thereby plays a crucial role in regulating iron homeostasis. BMP6 gene transcriptional regulation in liver is largely unknown, but would be of great help to externally modulate iron load in pathologic conditions. Here, we describe a detailed molecular mechanism of hepatic BMP6 gene expression by an orphan nuclear receptor, estrogen-related receptor γ (ERRγ), in response to the pro-inflammatory cytokine interleukin 6 (IL-6). Recombinant IL-6 treatment increases hepatic ERRγ and BMP6 expression. Overexpression of ERRγ is sufficient to increase BMP6 gene expression in hepatocytes, suggesting that IL-6 is upstream of ERRγ. In line, knock-down of ERRγ in cell lines or a hepatocyte specific knock-out of ERRγ in mice significantly decreases IL-6 mediated BMP6 expression. Promoter studies show that ERRγ directly binds to the ERR response element (ERRE) in the mouse BMP6 gene promoter and positively regulates BMP6 gene transcription in IL-6 treatment conditions, which is further confirmed by ERRE mutated mBMP6-luciferase reporter assays. Finally, an inverse agonist of ERRγ, GSK5182, markedly inhibits IL-6 induced hepatic BMP6 expression in vitro and in vivo. Taken together, these results reveal a novel molecular mechanism on ERRγ mediated transcriptional regulation of hepatic BMP6 gene expression in response to IL-6.

scholarly journals Orphan Nuclear Receptor ERRγ Is a Transcriptional Regulator of CB1 Receptor-Mediated TFR2 Gene Expression in Hepatocytes

2021 ◽  
Vol 22 (11) ◽  
pp. 6021
Author(s):  
Bo-Eun Kim ◽  
Byungyoon Choi ◽  
Woo-Ram Park ◽  
Yu-Ji Kim ◽  
In-Young Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Nuclear Receptor ◽  
Gene Transcription ◽  
Cannabinoid Receptor ◽  
Gene Promoter ◽  
Cb1 Receptor ◽  
Orphan Nuclear Receptor ◽  
Endocrine Control ◽  
Hepatic Iron Overload

Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is an important transcription factor modulating gene transcription involved in endocrine control of liver metabolism. Transferrin receptor 2 (TFR2), a carrier protein for transferrin, is involved in hepatic iron overload in alcoholic liver disease (ALD). However, TFR2 gene transcriptional regulation in hepatocytes remains largely unknown. In this study, we described a detailed molecular mechanism of hepatic TFR2 gene expression involving ERRγ in response to an endocannabinoid 2-arachidonoylglycerol (2-AG). Treatment with 2-AG and arachidonyl-2′-chloroethylamide, a selective cannabinoid receptor type 1 (CB1) receptor agonist, increased ERRγ and TFR2 expression in hepatocytes. Overexpression of ERRγ was sufficient to induce TFR2 expression in both human and mouse hepatocytes. In addition, ERRγ knockdown significantly decreased 2-AG or alcohol-mediated TFR2 gene expression in cultured hepatocytes and mouse livers. Finally, deletion and mutation analysis of the TFR2 gene promoter demonstrated that ERRγ directly modulated TFR2 gene transcription via binding to an ERR-response element. This was further confirmed by chromatin immunoprecipitation assay. Taken together, these results reveal a previously unrecognized role of ERRγ in the transcriptional regulation of TFR2 gene expression in response to alcohol.

scholarly journals Transcriptional Regulation of Apolipoprotein C-III Gene Expression by the Orphan Nuclear Receptor RORα

2000 ◽  
Vol 276 (4) ◽  
pp. 2865-2871 ◽  
Author(s):  
Eric Raspé ◽  
Hélène Duez ◽  
Phillippe Gervois ◽  
Catherine Fiévet ◽  
Jean-Charles Fruchart ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Nuclear Receptor ◽  
Orphan Nuclear Receptor ◽  
Apolipoprotein C
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