THE CGTCA SEQUENCE MOTIF IS ESSENTIAL FOR BIOLOGICAL-ACTIVITY OF THE VASOACTIVE INTESTINAL PEPTIDE GENE CAMP-REGULATED ENHANCER

THE CGTCA SEQUENCE MOTIF IS ESSENTIAL FOR BIOLOGICAL-ACTIVITY OF THE VASOACTIVE INTESTINAL PEPTIDE GENE CAMP-REGULATED ENHANCER
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DOI:
10.1073/pnas.85.18.6662
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发表时间:
1988-09-01
影响因子:
11.1
通讯作者:
GOODMAN, RH
GOODMAN, RH
中科院分区:
综合性期刊1区
文献类型:
--
作者:
FINK, JS;VERHAVE, M;GOODMAN, RH

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cAMP调节的人血管活性肠肽基因的转录依赖于位于转录起始位点上游70个碱基对的17个碱基对的DNA元件。该元件类似于已知由cAMP调节的其他基因中的序列和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个增强子,依赖于两个CGTCA序列基序的生物活性的完整性。CGTCA基序中的任何一个突变都会降低元件对cAMP的反应能力。含有生长抑素和腺病毒基因的CGTCA基序的增强子竞争C6胶质瘤和PC12细胞的核蛋白与血管活性肠肽增强子的结合,表明含有CGTCA的增强子与类似的反式因子相互作用。
cAMP-regulated transcription of the human vasoactive intestinal peptide gene is dependent upon a 17-basepair 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.