Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.

Research output: Contribution to journalJournal articlepeer-review

Standard

Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha. / Mortensen, Ole Hartvig; Dichmann, Darwin Sorento; Abrahamsen, Niels; Grunnet, Niels; Nishimura, Erica.

In: Gene, Vol. 393, No. 1-2, 2007, p. 127-36.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Mortensen, OH, Dichmann, DS, Abrahamsen, N, Grunnet, N & Nishimura, E 2007, 'Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.', Gene, vol. 393, no. 1-2, pp. 127-36. https://doi.org/10.1016/j.gene.2007.01.023

APA

Mortensen, O. H., Dichmann, D. S., Abrahamsen, N., Grunnet, N., & Nishimura, E. (2007). Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha. Gene, 393(1-2), 127-36. https://doi.org/10.1016/j.gene.2007.01.023

Vancouver

Mortensen OH, Dichmann DS, Abrahamsen N, Grunnet N, Nishimura E. Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha. Gene. 2007;393(1-2):127-36. https://doi.org/10.1016/j.gene.2007.01.023

Author

Mortensen, Ole Hartvig ; Dichmann, Darwin Sorento ; Abrahamsen, Niels ; Grunnet, Niels ; Nishimura, Erica. / Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha. In: Gene. 2007 ; Vol. 393, No. 1-2. pp. 127-36.

Bibtex

@article{3e04da00ab5811ddb5e9000ea68e967b,
title = "Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.",
abstract = "Previously we have demonstrated that glucagon receptor mRNA expression in cultured rat hepatocytes and pancreatic islets can be regulated by various factors, including cAMP; however, the regulation of the human glucagon receptor gene has not been well-defined. Here we have characterized the promoter regions of the human glucagon receptor gene. Primer extension studies yielded multiple products in both liver and pancreas, corresponding to transcription start sites situated at -166 and -477 relative to the start of translation, indicating two putative promoters. Both transcription start sites were found to be active, when sequence immediately upstream of the start sites were cloned into luciferase reporter constructs. The transcriptional activity of the proximal promoter, but not the distal promoter, could be inhibited approximately 50% by cAMP, indicating that the previously observed inhibitory effects of cAMP on glucagon receptor mRNA expression is mediated at the level of gene transcription. The cAMP-mediated downregulation of the proximal promoter was examined by deletion analysis in the human hepatoma cell line HepG2 and the cAMP responsiveness was found to be located in a region between 1051 and 1016 base pairs upstream of the transcription start site, which contains several putative cAMP responsive elements. Expression of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), known to be upregulated in the liver by fasting, was found to abolish the cAMP-dependent downregulation of glucagon receptor mRNA expression in vitro, whereas overexpression of PGC-1beta had no effect.",
author = "Mortensen, {Ole Hartvig} and Dichmann, {Darwin Sorento} and Niels Abrahamsen and Niels Grunnet and Erica Nishimura",
note = "Keywords: 5' Flanking Region; Base Sequence; Carrier Proteins; Cell Line, Tumor; Cyclic AMP; Gene Expression Regulation; Genes, Reporter; Heat-Shock Proteins; Humans; Molecular Sequence Data; Promoter Regions (Genetics); Receptors, Glucagon; Sequence Analysis, DNA; Time Factors; Transcription Factors; Transcription Initiation Site",
year = "2007",
doi = "10.1016/j.gene.2007.01.023",
language = "English",
volume = "393",
pages = "127--36",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",
number = "1-2",

}

RIS

TY - JOUR

T1 - Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.

AU - Mortensen, Ole Hartvig

AU - Dichmann, Darwin Sorento

AU - Abrahamsen, Niels

AU - Grunnet, Niels

AU - Nishimura, Erica

N1 - Keywords: 5' Flanking Region; Base Sequence; Carrier Proteins; Cell Line, Tumor; Cyclic AMP; Gene Expression Regulation; Genes, Reporter; Heat-Shock Proteins; Humans; Molecular Sequence Data; Promoter Regions (Genetics); Receptors, Glucagon; Sequence Analysis, DNA; Time Factors; Transcription Factors; Transcription Initiation Site

PY - 2007

Y1 - 2007

N2 - Previously we have demonstrated that glucagon receptor mRNA expression in cultured rat hepatocytes and pancreatic islets can be regulated by various factors, including cAMP; however, the regulation of the human glucagon receptor gene has not been well-defined. Here we have characterized the promoter regions of the human glucagon receptor gene. Primer extension studies yielded multiple products in both liver and pancreas, corresponding to transcription start sites situated at -166 and -477 relative to the start of translation, indicating two putative promoters. Both transcription start sites were found to be active, when sequence immediately upstream of the start sites were cloned into luciferase reporter constructs. The transcriptional activity of the proximal promoter, but not the distal promoter, could be inhibited approximately 50% by cAMP, indicating that the previously observed inhibitory effects of cAMP on glucagon receptor mRNA expression is mediated at the level of gene transcription. The cAMP-mediated downregulation of the proximal promoter was examined by deletion analysis in the human hepatoma cell line HepG2 and the cAMP responsiveness was found to be located in a region between 1051 and 1016 base pairs upstream of the transcription start site, which contains several putative cAMP responsive elements. Expression of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), known to be upregulated in the liver by fasting, was found to abolish the cAMP-dependent downregulation of glucagon receptor mRNA expression in vitro, whereas overexpression of PGC-1beta had no effect.

AB - Previously we have demonstrated that glucagon receptor mRNA expression in cultured rat hepatocytes and pancreatic islets can be regulated by various factors, including cAMP; however, the regulation of the human glucagon receptor gene has not been well-defined. Here we have characterized the promoter regions of the human glucagon receptor gene. Primer extension studies yielded multiple products in both liver and pancreas, corresponding to transcription start sites situated at -166 and -477 relative to the start of translation, indicating two putative promoters. Both transcription start sites were found to be active, when sequence immediately upstream of the start sites were cloned into luciferase reporter constructs. The transcriptional activity of the proximal promoter, but not the distal promoter, could be inhibited approximately 50% by cAMP, indicating that the previously observed inhibitory effects of cAMP on glucagon receptor mRNA expression is mediated at the level of gene transcription. The cAMP-mediated downregulation of the proximal promoter was examined by deletion analysis in the human hepatoma cell line HepG2 and the cAMP responsiveness was found to be located in a region between 1051 and 1016 base pairs upstream of the transcription start site, which contains several putative cAMP responsive elements. Expression of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha), known to be upregulated in the liver by fasting, was found to abolish the cAMP-dependent downregulation of glucagon receptor mRNA expression in vitro, whereas overexpression of PGC-1beta had no effect.

U2 - 10.1016/j.gene.2007.01.023

DO - 10.1016/j.gene.2007.01.023

M3 - Journal article

C2 - 17374560

VL - 393

SP - 127

EP - 136

JO - Gene

JF - Gene

SN - 0378-1119

IS - 1-2

ER -

ID: 8419157