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The contribution of E2F-regulated transcription to drosophila PCNA gene function

机译：E2F调控的转录对果蝇PCNA基因功能的贡献

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摘要

E2F proteins control cell cycle progression by predominantly acting as either activators or repressors of transcription [1]. How the antagonizing activities of different E2Fs are integrated by cis-acting control regions into a final transcriptional output in an intact animal is not well understood. E2F function is required for normal development in many species [2-7], but it is not completely clear for which genes E2F-regulated transcription provides an essential biological function. To address these questions, we have characterized the control region of the Drosophila PCNA gene. A single E2F binding site within a 100-bp enhancer is necessary and sufficient to direct the correct spatio-temporal program of G1-S-regulated PCNA expression during development. This dynamic program requires both E2F-mediated transcriptional activation and repression, which, in Drosophila, are thought to be carried out by two distinct E2F proteins [2,3,8-11]. Our data suggest that functional antagonism between these different E2F proteins can occur in vivo by competition for the same binding site. An engineered PCNA gene with mutated E2F binding sites supports a low level of expression that can partially rescue the lethality of PCNA null mutants. Thus, E2F regulation of PCNA is dispensable for viability, but is nonetheless important for normal Drosophila development.
机译：E2F蛋白主要通过充当转录激活因子或阻遏因子来控制细胞周期进程[1]。尚不清楚如何通过顺式作用控制区将不同的E2Fs的拮抗活性整合到最终的转录输出中。 E2F功能是许多物种正常发育所必需的[2-7]，但尚不清楚E2F调控的哪些基因提供必需的生物学功能。为了解决这些问题，我们已经表征了果蝇PCNA基因的控制区域。 100 bp增强子内的单个E2F结合位点是必要的，并且足以指导发育过程中G1-S调控的PCNA表达的正确时空程序。这个动态程序需要E2F介导的转录激活和抑制，在果蝇中，这被认为是由两种不同的E2F蛋白[2,3,8-11]进行的。我们的数据表明，这些不同的E2F蛋白之间的功能拮抗作用可以在体内通过竞争相同的结合位点而发生。具有突变的E2F结合位点的工程PCNA基因支持低水平的表达，可以部分挽救PCNA空突变体的致死性。因此，PCNA的E2F调节对于生存力是必不可少的，但对于正常的果蝇发育却很重要。

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