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首页> 外文期刊>Molecular and Cellular Biology >A role for a bent DNA structure in E2F-mediated transcription activation.
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A role for a bent DNA structure in E2F-mediated transcription activation.

机译：弯曲的DNA结构在E2F介导的转录激活中的作用。

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We examined the role of promoter architecture, as well as that of the DNA-bending capacity of the E2F transcription factor family, in the activation of transcription. DNA phasing analysis revealed that a consensus E2F site in the E2F1 promoter possesses an inherent bend with a net magnitude of 40 +/-2 degrees and with an orientation toward the major groove relative to the center of the E2F site. The inherent DNA bend is reversed upon binding of E2F, generating a net bend with a magnitude of 25 +/- 3 degrees oriented toward the minor groove relative to the center of the E2F site. We also found that three members of the E2F family, in conjunction with the DP1 protein, bend the DNA toward the minor groove, suggesting that DNA bending is a characteristic of the entire E2F family. The Rb-E2F complex, on the other hand, does not reverse the intrinsic DNA bend. Analysis of a series of E2F1 deletion mutants defined E2F1 sequences which are not required for DNA binding but are necessary for the DNA-bending capacity of E2F. An internal region of E2F1, previously termed the marked box, which is highly homologous among E2F family members, was particularly important in DNA bending. We also found that a bent DNA structure can be a contributory component in the activation of the E2F1 promoter but is not critical in the repression of that promoter in quiescent cells. This finding suggests that E2F exhibits characteristics typical of modular transcription factors, with independent DNA-binding and transcriptional activation functions, but also has features of architectural factors that alter DNA structure.
机译：我们检查了启动子结构的作用，以及E2F转录因子家族的DNA弯曲能力在转录激活中的作用。 DNA阶段分析显示，E2F1启动子中的共有E2F位点具有固有弯曲，其净幅度为40 +/- 2度，并且相对于E2F位点的中心朝向主要凹槽。当结合E2F时，固有的DNA弯曲被逆转，产生了一个相对于E2F部位的中心朝向次要凹槽定向为25 +/- 3度的净弯曲。我们还发现E2F家族的三个成员与DP1蛋白一起使DNA向着小沟弯曲，这表明DNA弯曲是整个E2F家族的特征。另一方面，Rb-E2F复合物不能逆转内在的DNA弯曲。对一系列E2F1缺失突变体的分析确定了E2F1序列，该序列不是DNA结合所必需的，但对于E2F的DNA弯曲能力而言是必需的。 E2F1的内部区域（以前称为标记框）在E2F家族成员之间高度同源，在DNA弯曲中特别重要。我们还发现，弯曲的DNA结构可以是E2F1启动子激活的一个重要组成部分，但在静止细胞中抑制该启动子方面并不关键。这一发现表明，E2F具有典型的模块化转录因子特征，具有独立的DNA结合和转录激活功能，而且还具有改变DNA结构的建筑因子特征。

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