Fink J S, Verhave M, Kasper S, Tsukada T, Mandel G, Goodman R H
Department of Medicine, New England Medical Center Hospital, Boston, MA 02111.
Proc Natl Acad Sci U S A. 1988 Sep;85(18):6662-6. doi: 10.1073/pnas.85.18.6662.
cAMP-regulated transcription of the human vasoactive intestinal peptide gene is dependent upon a 17-base-pair DNA element located 70 base pairs upstream from the transcriptional initiation site. This element is similar to sequences in other genes known to be regulated by cAMP and to sequences in several viral enhancers. We have demonstrated that the vasoactive intestinal peptide regulatory element is an enhancer that depends upon the integrity of two CGTCA sequence motifs for biological activity. Mutations in either of the CGTCA motifs diminish the ability of the element to respond to cAMP. Enhancers containing the CGTCA motif from the somatostatin and adenovirus genes compete for binding of nuclear proteins from C6 glioma and PC12 cells to the vasoactive intestinal peptide enhancer, suggesting that CGTCA-containing enhancers interact with similar transacting factors.
人血管活性肠肽基因的cAMP调节转录依赖于位于转录起始位点上游70个碱基对处的一个17碱基对的DNA元件。该元件类似于已知受cAMP调节的其他基因中的序列以及几种病毒增强子中的序列。我们已经证明,血管活性肠肽调节元件是一种增强子,其生物学活性依赖于两个CGTCA序列基序的完整性。任一CGTCA基序中的突变都会削弱该元件对cAMP作出反应的能力。含有来自生长抑素和腺病毒基因的CGTCA基序的增强子竞争C6胶质瘤细胞和PC12细胞的核蛋白与血管活性肠肽增强子的结合,这表明含CGTCA的增强子与相似的反式作用因子相互作用。