Contribution of a PS1-like element to the tissue- and cell-specific expression of the human GLP-1 receptor gene.
The GLP-1 receptor (GLP-1R) mediates the insulinotropic effects of the incretion hormone glucagon-like peptide 1 (7-36) amide (GLP-1). Recently, we cloned the 5'-flanking region of the human GLP-1R gene. To characterize tissue- and cell-specific cis-regulatory elements, we constructed a series of 5'-deletions of the promoter. The activity of these constructs was tested in different cell lines. An element with high homology to PS1 was found to repress GLP-1R promoter activity in fibroblasts and pancreatic D-cells, but was not active in pancreatic A- and B-cells. PS1 was described to inhibit activation of a D-cell-specific enhancer. Cloning the PS1-like element upstream a heterologous promoter (SV40) revealed that it is functionally active independently from this enhancer. Our data suggest that basal activity of the GLP-1R promoter is silenced in a tissue- and cell-specific manner by negatively acting cis-regulatory elements, including a PS1-like element.
Clinical Research Unit for Gastrointestinal Endocrinology, Philipps-University of Marburg, Germany.
F S
FS
Galehshahi
B
B
Göke
B
B
Lankat-Buttgereit
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D005935:Glucagonoma; D006801:Humans; D007340:Insulinoma; D007515:Islets of Langerhans / Q000378:metabolism; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009928:Organ Specificity; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000378:metabolism; D018027:Receptors, Glucagon / Q000096:biosynthesis / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D011994:Recombinant Proteins; D052216:Glucagon-Like Peptide 1; D005934:Glucagon