Functional antagonism between E2F family members
Functional antagonism between E2F family members
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DOI：
10.1101/gad.903901
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发表时间：
2001-08-15
影响因子：
10.5
通讯作者：
Dyson, NJ
中科院分区：
文献类型：
--
作者：
Frolov, MV;Huen, DS;Dyson, NJ
E2 F是一种异源性转录因子，其在细胞周期调控中的作用是由许多不同E2 F家族成员的整合活性决定的。与有大量E2 F相关基因的哺乳动物细胞不同，果蝇基因组只编码两个E2 F基因，de 2f 1和de 2f 2。在这里，我们表明，de 2f 1和de 2f 2提供E2 F调节的不同元素，它们在果蝇发育过程中具有相反的功能。dE 2F 1和dE 2F 2均与DDP异源二聚体化，并在体内与E2 F调节基因的启动子结合。dE 2F 1是一种有效的转录激活因子，de 2f 1的缺失导致E2 F调控基因的表达减少。相反，dE 2F 2抑制E2 F报告基因的转录，并且de 2f 2功能的丧失导致基因表达模式的增加和扩展。先前已经报道了de 2f 1功能的丧失会损害细胞增殖。de 2f 1突变胚胎E2 F调节基因的表达减少，DNA合成水平低，孵化出生长缓慢的幼虫。我们发现，这些缺陷在很大程度上是由于dE 2F 2的活性未经检查，因为它们可以通过de 2f 2的突变来抑制。对de 2f 1; de 2f 2双突变动物的眼盘检查表明，在两种E2 F蛋白都不存在的情况下，可以发生相对正常的DNA合成模式。这项研究显示了阻遏物和激活剂E2 Fs如何用于转录模式，以及E2 F对细胞增殖的净效应如何来自具有拮抗功能的两种类型的E2 F复合物之间的相互作用。
E2F is a heterogenous transcription factor and its role in cell cycle control results from the integrated activities of many different E2F family members. Unlike mammalian cells, that have a large number of E2F-related genes, the Drosophila genome encodes just two E2F genes, de2f1 and de2f2. Here we show that de2f1 and de2f2 provide different elements of E2F regulation and that they have opposing functions during Drosophila development. dE2F1 and dE2F2 both heterodimerize with dDP and bind to the promoters of E2F-regulated genes in vivo. dE2F1 is a potent activator of transcription, and the loss of de2f1 results in the reduced expression of E2F-regulated genes. In contrast, dE2F2 represses the transcription of E2F reporters and the loss of de2f2 function results in increased and expanded patterns of gene expression. The loss of de2f1 function has previously been reported to compromise cell proliferation. de2f1 mutant embryos have reduced expression of E2F-regulated genes, low levels of DNA synthesis, and hatch to give slow-growing larvae. We find that these defects are due in large part to the unchecked activity of dE2F2, since they can be suppressed by mutation of de2f2. Examination of eye discs from de2f1; de2f2 double-mutant animals reveals that relatively normal patterns of DNA synthesis can occur in the absence of both E2F proteins. This study shows how repressor and activator E2Fs are used to pattern transcription and how the net effect of E2F on cell proliferation results from the interplay between two types of E2F complexes that have antagonistic functions.