A novel silencer element repressing expression of the GLP-1 receptor gene in fibroblasts and pancreatic A-cells, but not in pancreatic B- and D-cells.
The effects of the incretin hormone glucagon-like peptide 1 (7-36)amide (GLP-1) are mediated by the GLP-1 receptor (GLP-1R). This is expressed in a cell- and tissue-specific manner. Recently, we have cloned the 5'-flanking region of the human GLP-1R gene. The basal promoter activity is driven by the ubiquitous transcription factor Sp1. The tissue- and cell-specific expression of the gene requires several negatively acting cis-regulatory elements. We have now characterized one so far unknown distal cell-specific silencer element (DCS), repressing gene transcription of the human GLP-1R gene in fibroblasts and pancreatic A-cells, but not in pancreatic B- and D-cells. Our data suggests that the basal activity of the GLP-1R promoter is repressed in a tissue- and cell-specific manner by this novel silencer element.
Galehshahi
F S
FS
Clinical Research Unit for Gastrointestinal Endocrinology, Philipps-University of Marburg, Baldingerstr., D-35033 Marburg, Germany.
Göke
B
B
Lankat-Buttgereit
B
B
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D003432:Cross-Linking Reagents; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts / Q000378:metabolism*; D017353:Gene Deletion; D020868:Gene Silencing; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D018027:Receptors, Glucagon / Q000096:biosynthesis* / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014018:Tissue Distribution; D014158:Transcription, Genetic; D014162:Transfection; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D016329:Sp1 Transcription Factor; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D008156:Luciferases; D003850:Deoxyribonuclease I