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首页> 外文期刊>Molecular and Cellular Biology >Multiple sequence elements of a single functional class are required for cyclic AMP responsiveness of the mouse c-fos promoter.
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Multiple sequence elements of a single functional class are required for cyclic AMP responsiveness of the mouse c-fos promoter.

机译：小鼠c-fos启动子的环AMP响应性需要单个功能类别的多个序列元件。

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摘要

Agents that elevate the intracellular concentration of cyclic AMP (cAMP) rapidly and transiently induce expression of the c-fos proto-oncogene in BALB/c 3T3 cells. We show that the mouse c-fos promoter-enhancer region contains multiple elements that contribute to cAMP responsiveness of the promoter in transient expression assays. The most potent element was found to correspond to a previously mapped basal promoter element and protein-binding site located 65 base pairs upstream of the transcriptional initiation site. This element and two less potent sites contained a match to the cAMP response element (CRE) core sequence defined in several mammalian genes. The relative potencies of these elements corresponded with their relative affinities for cellular factors that bound to the CRE in vitro. Mutation of all three elements failed to abolish completely cAMP responsiveness of the c-fos promoter in the transient expression assay. However, we present evidence that this residual responsiveness may have been due to sequences present in vector DNA. Finally, we show, by using a new microinjection competition assay, that a double-stranded oligonucleotide carrying the major c-fos CRE is sufficient to block induction of the endogenous c-fos gene by cAMP. Therefore, induction of the endogenous gene requires positively acting cellular factors that interact with a single functional class of regulatory sites in the c-fos gene. Unrelated regulatory elements, such as the serum response element and putative AP-2 sites, are not by themselves sufficient to mediate the cAMP response.
机译：快速升高细胞内环AMP（cAMP）浓度的药物可瞬时诱导BALB / c 3T3细胞中c-fos原癌基因的表达。我们显示，小鼠c-fos启动子增强子区域包含多个元素，这些元素在瞬时表达测定中有助于启动子的cAMP响应性。发现最有效的元件对应于先前定位的基础启动子元件和位于转录起始位点上游65个碱基对的蛋白质结合位点。该元件和两个较低效位点包含与几个哺乳动物基因中定义的cAMP反应元件（CRE）核心序列的匹配。这些元素的相对效力与其在体外与CRE结合的细胞因子的相对亲和力相对应。在瞬时表达测定中，所有这三个元件的突变均不能完全消除c-fos启动子的cAMP反应性。但是，我们提供的证据表明这种残留的响应性可能是由于载体DNA中存在的序列所致。最后，我们显示，通过使用新的显微注射竞争试验，带有主要c-fos CRE的双链寡核苷酸足以阻止cAMP对内源性c-fos基因的诱导。因此，内源基因的诱导需要与c-fos基因中单一功能类别的调控位点相互作用的正性细胞因子。无关的调节元件，例如血清反应元件和推定的AP-2位点，本身不足以介导cAMP反应。

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