The POU domain transcription factor Tst-1 activates somatostatin receptor 1 gene expression in pancreatic beta -cells.
The peptide hormone somatostatin inhibits the release of insulin. The gene encoding somatostatin receptor 1 is expressed in pancreatic beta-cells and insulinoma RIN 1046-38 cells. In the present study the mechanisms underlying the regulation of the somatostatin receptor 1 gene in pancreatic beta-cells were investigated. Transient transfections of RIN 1046-38 cells with promoter/reporter gene constructs and footprint analysis revealed two regions, fp1 and fp2, that were necessary for the observed promoter activity. Mutagenesis of the fp2 region delineated the cis-acting element to the motif 5'-TTAATCATT-3'. The POU domain transcription factor Tst-1 was identified as trans-activator mediating the 5'-TTAATCATT-3' motif-dependent transcription in RIN 1046-38 cells and heterologous CV1 cells. Tst-1, known as a transcriptional regulator in keratinocytes, glial cells, and neurons, has been detected by immunohistochemistry in pancreatic islets. Altogether, we demonstrate Tst-1 as transcriptional regulator in pancreatic neuroendocrine cells.
Baumeister
H
H
Abteilung Molekulare Genetik, Deutsches Institut für Ernährungsforschung und Universität Potsdam, Arthur-Scheunert-Allee 114-116, D-14558 Potsdam-Rehbrücke, Germany.
Meyerhof
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W
D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation; D051863:Host Cell Factor C1; D007515:Islets of Langerhans / Q000378:metabolism*; D050811:Octamer Transcription Factor-1; D050816:Octamer Transcription Factor-6; D011401:Promoter Regions, Genetic; D051381:Rats; D017481:Receptors, Somatostatin / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D051863:Host Cell Factor C1; D050811:Octamer Transcription Factor-1; C494168:Pou2f1 protein, rat; C494179:Pou3f1 protein, rat; D017481:Receptors, Somatostatin; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6; D004247:DNA