Galehshahi F S, Göke B, Lankat-Buttgereit B
Clinical Research Unit for Gastrointestinal Endocrinology, Philipps-University of Marburg, Germany.
FEBS Lett. 1998 Oct 2;436(2):163-8. doi: 10.1016/s0014-5793(98)01116-8.
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.
胰高血糖素样肽-1受体（GLP-1R）介导肠促胰岛素激素胰高血糖素样肽1（7-36）酰胺（GLP-1）的促胰岛素作用。最近，我们克隆了人GLP-1R基因的5'侧翼区。为了鉴定组织和细胞特异性顺式调控元件，我们构建了一系列启动子的5'缺失体。在不同细胞系中检测了这些构建体的活性。发现一个与PS1具有高度同源性的元件在成纤维细胞和胰腺D细胞中抑制GLP-1R启动子活性，但在胰腺A细胞和B细胞中无活性。PS1被描述为抑制D细胞特异性增强子的激活。在异源启动子（SV40）上游克隆PS1样元件表明，它在功能上独立于该增强子发挥作用。我们的数据表明，GLP-1R启动子的基础活性通过包括PS1样元件在内的负性作用顺式调控元件以组织和细胞特异性方式被沉默。
