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Adenovirus E1a proteins repress expression from polyomavirus early and late promoters.

机译:腺病毒E1a蛋白抑制多瘤病毒早期和晚期启动子的表达。

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We have examined the effects of the E1a products of adenovirus types 5 and 12 on the expression of polyomavirus early and late promoters. In cotransfection experiments in HeLa cells, plasmids expressing the E1a region of adenovirus type 5 or 12 repressed both the early and late promoters of polyomavirus, and deletion analysis indicates that the polyomavirus enhancers were the target of the E1a repression. With mutants lacking enhancer sequences, the polyomavirus early promoter but not the late promoter was trans-activated by E1a. Chimeric mutant plasmids with deletions in the regulatory region that contained either the A enhancer or the B enhancer were repressed to the same extent, indicating that E1a can repress both elements. Polyomavirus variant plasmids with rearrangements in the regulatory region conferring activity in embryonal carcinoma stem cells were repressed by E1a as was the wild type, suggesting that the repressor function is quite general. We discuss a model in which the influence of E1a on the transcriptional activity of a gene is the sum of positive and negative effects on promoter and enhancer elements and discuss possible mechanisms of negative regulation of enhancer function.
机译:我们已经检查了5型和12型腺病毒的E1a产物对多瘤病毒早期和晚期启动子表达的影响。在HeLa细胞中的共转染实验中,表达5型或12型腺病毒E1a区的质粒抑制多瘤病毒的早期和晚期启动子,缺失分析表明多瘤病毒增强子是E1a抑制的目标。对于缺少增强子序列的突变体,多瘤病毒的早期启动子而不是晚期启动子被E1a反式激活。在含有A增强子或B增强子的调控区中缺失的嵌合突变质粒被抑制到相同程度,表明E1a可以抑制两个元件。与野生型一样,E1a抑制了在胚胎癌细胞干细胞中赋予活性的调控区中重排的多瘤病毒变体质粒,这表明阻遏物的功能十分普遍。我们讨论了一个模型,其中E1a对基因的转录活性的影响是对启动子和增强子元件的正向和负向影响的总和,并讨论了负向调节增强子功能的可能机制。

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