Cell type specific regulation of COUP‐TF II promoter activity

Soosaar, Andres; Neuman, K.; Nornes, Howard O.; Neuman, Toomas

doi:10.1016/0014-5793(96)00711-9

Cited by 12 publications

(10 citation statements)

References 37 publications

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“…COUP-TFs are believed to influence developmental changes, which is supported by the report that the COUP-TFII promoter responds to differentiation signal, retinoic acid (17). Recently, we have mapped a complex retinoic acid response region located between Ϫ176 and Ϫ117 of the rat CYP7A promoter (10).…”

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confidence: 53%

Orphan Receptors Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) and Retinoid X Receptor (RXR) Activate and Bind the Rat Cholesterol 7α-Hydroxylase Gene (CYP7A)

Stroup

Crestani

Chiang

1997

Journal of Biological Chemistry

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The cholesterol 7␣-hydroxylase gene (CYP7A) is transcriptionally regulated by a number of factors, including hormones, bile acids, and diurnal rhythm. Previous studies have identified a region from nucleotides (nt) ؊74 to ؊55 of the rat CYP7A promoter that enhanced bile acid repression of the SV40 early promoter, as assayed with a luciferase reporter gene in transiently transfected HepG2 cells. The rat CYP7A promoter/reporter activity was strongly stimulated by cotransfection with an expression plasmid encoding the nuclear hormone receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) in a dose-dependent manner. Site-directed mutagenesis in the region of nt ؊74 to ؊55 altered this stimulation. Recombinant COUP-TFII expressed in HepG2 or COS-1 cells were found to bind to nt ؊74 ؊55 and nt ؊149 ؊128 probes by electrophoretic mobility shift assay (EMSA) and by supershifting the corresponding band with COUP-TFII-specific antibodies. The region of nt ؊176 ؊117 was previously mapped as a retinoic acid response region and was found to bind retinoid X receptor (RXR). EMSA supershift assays of wild-type and mutant oligomers using antibody against RXR revealed that the sequences between nt ؊145 and ؊134 were important for RXR binding. We conclude that COUP-TFII stimulates the transcriptional activity of the rat CYP7A promoter by binding to the sequences between nt ؊74 to ؊54 and nt ؊149 to ؊128. RXR may stimulate CYP7A gene transcription by binding to a direct repeat of the hormone response element separated by one nucleotide located at nt ؊146 ؊134.Cholesterol 7␣-hydroxylase (EC 1.14.13.17) catalyzes the first and rate-limiting step in a pathway that converts cholesterol to bile acids. The catabolism of cholesterol to bile acids in the liver is the main mechanism for elimination of cholesterol from the body and thus plays an important role in maintaining cholesterol homeostasis (1). The gene CYP7A is transcriptionally regulated by a number of factors, including bile acids, cholesterol, hormones, and circadian rhythm (2-6).The CYP7A promoter structure is typical of a DNA-dependent RNA polymerase II promoter in that, upstream of the TATA box, there are several cis-acting elements that regulate the transcriptional activity of this promoter (7-9). Transient transfection assay of chimeric CYP7A promoter/luciferase constructs in HepG2 cells revealed that the region from nt Ϫ416 to ϩ32 of the rat CYP7A gene contained the promoter and regulatory domains conferring the activation of transcription by dexamethasone and retinoic acid and suppression by bile acids, phorbol esters, and insulin (2, 3, 9, 10). We have mapped two footprints that are protected from DNase I digestion using rat liver nuclear extracts (11). Footprint (Fp) 1 A is located between nt Ϫ81 and Ϫ35, and FpB is located between nt Ϫ148 and Ϫ129. Nucleotide sequences in these two regions are highly conserved among homologous CYP7A genes of different species. These footprints contain liver-enriched transcription factors binding sites and ho...

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mentioning

confidence: 53%

Orphan Receptors Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) and Retinoid X Receptor (RXR) Activate and Bind the Rat Cholesterol 7α-Hydroxylase Gene (CYP7A)

Stroup

Crestani

Chiang

1997

Journal of Biological Chemistry

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“…The reporter plasmid Ϫ3000/luc (corresponding to positions Ϫ3047 to ϩ873 relative to the defined COUP-TFII gene transcription initiation site [20]) from the fragment described previously (27) was subcloned into the pGL3-Basic vector (Promega) by using BamHI/BglII restriction sites. Then fragments from Ϫ688 (EcoRI), Ϫ328 (ApaI), Ϫ48 (SacI), ϩ202 (FspI), ϩ418 (ApaI), and ϩ639 (SacI) to ϩ873 relative to the transcription initiation site were subcloned into the pGL3-Basic plasmid.…”

Section: Methodsmentioning

confidence: 99%

The MODY1 Gene for Hepatocyte Nuclear Factor 4α and a Feedback Loop Control COUP-TFII Expression in Pancreatic Beta Cells

Perilhou

Tourrel-Cuzin

Zhang

et al. 2008

Molecular and Cellular Biology

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Pancreatic islet beta cell differentiation and function are dependent upon a group of transcription factors that maintain the expression of key genes and suppress others. Knockout mice with the heterozygous deletion of the gene for chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) or the complete disruption of the gene for hepatocyte nuclear factor 4␣ (HNF4␣) in pancreatic beta cells have similar insulin secretion defects, leading us to hypothesize that there is transcriptional cross talk between these two nuclear receptors. Here, we demonstrate specific HNF4␣ activation of a reporter plasmid containing the COUP-TFII gene promoter region in transfected pancreatic beta cells. The stable association of the endogenous HNF4␣ with a region of the COUP-TFII gene promoter that contains a direct repeat 1 (DR-1) binding site was revealed by chromatin immunoprecipitation. Mutation experiments showed that this DR-1 site is essential for HNF4␣ transactivation of COUP-TFII. The dominant negative suppression of HNF4␣ function decreased endogenous COUP-TFII expression, and the specific inactivation of COUP-TFII by small interfering RNA caused HNF4␣ mRNA levels in 832/13 INS-1 cells to decrease. This positive regulation of HNF4␣ by COUP-TFII was confirmed by the adenovirus-mediated overexpression of human COUP-TFII (hCOUP-TFII), which increased HNF4␣ mRNA levels in 832/13 INS-1 cells and in mouse pancreatic islets. Finally, hCOUP-TFII overexpression showed that there is direct COUP-TFII autorepression, as COUP-TFII occupies the proximal DR-1 binding site of its own gene in vivo. Therefore, COUP-TFII may contribute to the control of insulin secretion through the complex HNF4␣/maturity-onset diabetes of the young 1 (MODY1) transcription factor network operating in beta cells.Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII, also called NR2F2) is an orphan member of the steroid/thyroid hormone receptor superfamily classed in the same subfamily as hepatocyte nuclear factor 4␣ (HNF4␣)/ maturity-onset diabetes of the young 1 (MODY1) and retinoid X receptor (RXR) (4, 11). Several molecular mechanisms by which COUP-TFII controls gene expression in pancreatic islet beta cell differentiation and function have been shown previously. COUP-TFII binds DNA by a Zn finger DNA binding domain in a variety of hormone response elements (HRE) that contain imperfect AGGTCA direct or inverted repeats with various spacing patterns (3, 14). It can form heterodimeric complexes with RXR, the universal partner of many nuclear receptors, and as such acts as a repressor (15). We previously showed that COUP-TFII acts as an inhibitor of the glucose activation of the liver pyruvate kinase gene by binding to the glucose-responsive element (9). On most promoters, HNF4␣ response elements are also bound by COUP-TFII, which often behaves as a transcriptional repressor antagonizing the enhancement of transcription by HNF4␣ (8,12,24). In a functional study, the impaired synergy between COUP-TFII and the E276Q mutant form of...

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“…MC3/4-R belongs to the family of G protein-coupled seven-transmembrane-domain receptors and the binding of its agonist induces an increased cAMP production [30]. A COUP-TFII gene promoter analysis had identified cAMP response element localized in the first 300 bp from the transcription start site [31]. In our hypothalamic cell line it did drive also the cAMP dependant activation of the COUP-TFII gene.…”

Section: Discussionmentioning

confidence: 60%

“…[31] had identified a functional cAMP response element (CRE) binding site in the promoter region of the mouse COUP-TFII gene. Following this observation, we asked whether cAMP had a direct transcriptional effect on the COUP-TFII gene promoter in an hypothalamic cell line.…”

Section: Resultsmentioning

confidence: 99%

The Nutritional Induction of COUP-TFII Gene Expression in Ventromedial Hypothalamic Neurons Is Mediated by the Melanocortin Pathway

Sabra-Makke

Tourrel-Cuzin²,

Denis³

et al. 2010

PLoS ONE

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BackgroundThe nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues.Methodology/Principal FindingsUsing hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression.Conclusions/SignificanceThese observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation.

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Cell type specific regulation of COUP‐TF II promoter activity

Cited by 12 publications

References 37 publications

Orphan Receptors Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) and Retinoid X Receptor (RXR) Activate and Bind the Rat Cholesterol 7α-Hydroxylase Gene (CYP7A)

Orphan Receptors Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII) and Retinoid X Receptor (RXR) Activate and Bind the Rat Cholesterol 7α-Hydroxylase Gene (CYP7A)

The MODY1 Gene for Hepatocyte Nuclear Factor 4α and a Feedback Loop Control COUP-TFII Expression in Pancreatic Beta Cells

The Nutritional Induction of COUP-TFII Gene Expression in Ventromedial Hypothalamic Neurons Is Mediated by the Melanocortin Pathway

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