Andersen F G, Jensen J, Heller R S, Petersen H V, Larsson L I, Madsen O D, Serup P
Department of Developmental Biology, Hagedorn Research Institute, Gentofte, Denmark.
FEBS Lett. 1999 Feb 26;445(2-3):315-20. doi: 10.1016/s0014-5793(99)00144-1.
The somatostatin upstream enhancer (SMS-UE) is a highly complex enhancer element. The distal A-element contains overlapping Pdx1 and Pbx binding sites. However, a point mutation in the A-element that abolishes both Pdxl and Pbx binding does not impair promoter activity. In contrast, a point mutation that selectively eliminates Pdx1 binding to a proximal B-element reduces the promoter activity. The B-element completely overlaps with a Pax6 binding site, the C-element. A point mutation in the C-element demonstrates that Pax6 binding is essential for promoter activity. Interestingly, a block mutation in the A-element reduces both Pax6 binding and promoter activity. In heterologous cells, Pdx1 potentiated Pax6 mediated activation of a somatostatin reporter. We conclude that the beta/delta-cell-specific activity of the SMS-UE is achieved through simultaneous binding of Pdx1 and Pax6 to the B- and C-elements, respectively. Furthermore, the A-element appears to stabilise Pax6 binding.
生长抑素上游增强子（SMS-UE）是一种高度复杂的增强子元件。远端A元件包含重叠的Pdx1和Pbx结合位点。然而，A元件中的一个点突变消除了Pdx1和Pbx的结合，但并不损害启动子活性。相反，一个选择性消除Pdx1与近端B元件结合的点突变会降低启动子活性。B元件与一个Pax6结合位点C元件完全重叠。C元件中的一个点突变表明Pax6结合对于启动子活性至关重要。有趣的是，A元件中的一个阻断突变会降低Pax6结合和启动子活性。在异源细胞中，Pdx1增强了Pax6介导的生长抑素报告基因的激活。我们得出结论，SMS-UE的β/δ细胞特异性活性是通过Pdx1和Pax6分别同时结合到B元件和C元件来实现的。此外，A元件似乎稳定了Pax6的结合。
