Isolation of pig mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene promoter: characterization of a peroxisome proliferator-responsive element

Low expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase gene during development correlates with an unusually low hepatic ketogenic capacity and lack of hyperketonaemia in piglets. Here we report the isolation and characterization of the 5´ end of the pig mitochondrial HMG-CoA synthase gene. The 581 bp region proximal to the transcription start site permits transcription of a reporter gene, confirming the function of the promoter. The pig mitochondrial HMG-CoA synthase promoter is trans-activated by the peroxisomal proliferator-activated receptor (PPAR), and a functional response element for PPAR (PPRE) has been localized in the promoter region. Pig PPRE is constituted by an imperfect direct repeat (DR-1) and a downstream sequence, both of which are needed to confer PPAR-sensitivity to a thymidine kinase promoter and to form complexes with PPAR·retinoid X receptor heterodimers. A role of PPAR trans-activation in starvation-associated induction of gene expression is suggested.

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Identification and characterization of a 3',5'-cyclic adenosine monophosphate-responsive element in the human corticotropin-releasing hormone gene promoter.

Molecular Endocrinology ◽

10.1210/mend.6.11.1480179 ◽

1992 ◽

Vol 6 (11) ◽

pp. 1931-1941 ◽

Cited By ~ 2

Author(s):

D Spengler ◽

R Rupprecht ◽

L P Van ◽

F Holsboer

Keyword(s):

Gene Promoter ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Corticotropin Releasing Hormone ◽

Releasing Hormone ◽

Responsive Element ◽

Identification And Characterization

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Characterization of a Putative Insulin-Responsive Element and Its Binding Protein(s) in Rat Angiotensinogen Gene Promoter: Regulation by Glucose and Insulin*

Endocrinology ◽

10.1210/endo.142.6.8214 ◽

2001 ◽

Vol 142 (6) ◽

pp. 2577-2585 ◽

Cited By ~ 14

Author(s):

Xing Chen ◽

Shao-Ling Zhang ◽

Li Pang ◽

Janos G. Filep ◽

Shiow-Shih Tang ◽

...

Keyword(s):

Binding Protein ◽

Gene Promoter ◽

Protein S ◽

Promoter Regulation ◽

Angiotensinogen Gene ◽

Responsive Element

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Regulation of IGFBP-2 expression during fasting

Biochemical Journal ◽

10.1042/bj20141248 ◽

2015 ◽

Vol 467 (3) ◽

pp. 453-460 ◽

Cited By ~ 10

Author(s):

Hye Suk Kang ◽

Mi-Young Kim ◽

Seung-Jae Kim ◽

Jae-Ho Lee ◽

Yong-Deuk Kim ◽

...

Keyword(s):

Gene Expression ◽

Gene Promoter ◽

Biological Action ◽

Peroxisome Proliferator ◽

Cultured Hepatocytes ◽

Peroxisome Proliferator Activated Receptor ◽

Akt Phosphorylation ◽

Primary Cultured Hepatocytes ◽

Igf Binding ◽

Responsive Element

Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2), one of the most abundant circulating IGFBPs, is known to attenuate the biological action of IGF-1. Although the effect of IGFBP-2 in preventing metabolic disorders is well known, its regulatory mechanism remains unclear. In the present study, we demonstrated the transcriptional regulation of the Igfbp-2 gene by peroxisome-proliferator-activated receptor (PPAR) α in the liver. During fasting, both Igfbp-2 and PPARα expression levels were increased. Wy14643, a selective PPARα agonist, significantly induced Igfbp-2 gene expression in primary cultured hepatocytes. However, Igfbp-2 gene expression in Pparα null mice was not affected by fasting or Wy14643. In addition, through transient transfection and chromatin immunoprecipitation assay in fasted livers, we determined that PPARα bound to the putative PPAR-responsive element between −511 bp and −499 bp on the Igfbp-2 gene promoter, indicating that the Igfbp-2 gene transcription is activated directly by PPARα. To explore the role of PPARα in IGF-1 signalling, we treated primary cultured hepatocytes with Wy14643 and observed a decrease in the number of IGF-1 receptors (IGF-1Rs) and in Akt phosphorylation. No inhibition was observed in the hepatocytes isolated from Pparα null mice. These results suggest that PPARα controls IGF-1 signalling through the up-regulation of hepatic Igfbp-2 transcription during fasting and Wy14643 treatment.

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Bcl3 Interacts Cooperatively with Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Coactivator 1α To Coactivate Nuclear Receptors Estrogen-Related Receptor α and PPARα

Molecular and Cellular Biology ◽

10.1128/mcb.01669-08 ◽

2009 ◽

Vol 29 (15) ◽

pp. 4091-4102 ◽

Cited By ~ 28

Author(s):

John Yang ◽

R. Sanders Williams ◽

Daniel P. Kelly

Keyword(s):

Energy Metabolism ◽

Nuclear Receptor ◽

Transcriptional Profiling ◽

Gene Promoter ◽

Pyruvate Dehydrogenase Kinase ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Cellular Energy ◽

Cellular Energy Metabolism ◽

Responsive Element

ABSTRACT Estrogen-related receptors (ERRs) play critical roles in regulation of cellular energy metabolism in response to inducible coactivators such as peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC-1α). A yeast two-hybrid screen led to the identification of the cytokine-stimulated transcriptional regulator, Bcl3, as an ERRα coactivator. Bcl3 was shown to synergize with PGC-1α to coactivate ERRα. Chromatin immunoprecipitation studies demonstrated that ERRα, PGC-1α, and Bcl3 form a complex on an ERRα-responsive element within the pyruvate dehydrogenase kinase 4 gene promoter in cardiac myocytes. Mapping studies demonstrated that Bc13 interacts with PGC-1α and ERRα, allowing for interaction with both proteins. Transcriptional profiling demonstrated that Bcl3 activates genes involved in diverse pathways including a subset involved in cellular energy metabolism known to be regulated by PGC-1α, ERRα, and a second nuclear receptor, PPARα. Consistent with the gene expression profiling results, Bcl3 was shown to synergistically coactivate PPARα with PGC-1α in a manner similar to ERRα. We propose that the cooperativity between Bcl3 and PGC-1α may serve as a point of convergence on nuclear receptor targets to direct programs orchestrating inflammatory and energy metabolism responses in heart and other tissues.

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