Muñoz Estela, Brewer Michelle, Baler Ruben
Unit on Temporal Gene Expression, Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
J Biol Chem. 2002 Sep 27;277(39):36009-17. doi: 10.1074/jbc.M203909200. Epub 2002 Jul 18.
The E-Box is a widely used DNA control element. Despite its brevity and broad distribution the E-Box is a remarkably versatile sequence that affects many different genetic programs, including proliferation, differentiation, tissue-specific responses, and cell death. The circadian clock is one of the latest pathways shown to employ this element. In this context, E-Boxes are likely to play a key role in establishing the robust waves of gene expression characteristic of circadian transcription. The regulatory flexibility of the E-Box hinges on the sequence ambiguity allowed at its core, the strong influence of the surrounding sequences, and the recruitment of spatially and temporally regulated E-Box-binding factors. Therefore, understanding how a particular E-Box can accomplish a specific task entails the identification and systematic analysis of these cis- and trans-acting E-Box modifiers. In the present study we compared the E-Box-containing minimal promoters of vasopressin and cyclin B1, two genes that can respond to the transcriptional oscillators driving the circadian clock and cell cycle, respectively. Results of this comparison will help elucidate the manner in which discreet DNA modules associate to either augment or restrain the activation of potential circadian E-Boxes in response to competing regulatory signals.
E盒是一种广泛使用的DNA控制元件。尽管其简短且分布广泛，但E盒是一种非常通用的序列，可影响许多不同的遗传程序，包括增殖、分化、组织特异性反应和细胞死亡。生物钟是最新显示使用该元件的途径之一。在这种情况下，E盒可能在建立昼夜节律转录特有的强大基因表达波中起关键作用。E盒的调节灵活性取决于其核心允许的序列模糊性、周围序列的强烈影响以及空间和时间调节的E盒结合因子的募集。因此，了解特定的E盒如何完成特定任务需要对这些顺式和反式作用的E盒修饰剂进行鉴定和系统分析。在本研究中，我们比较了血管加压素和细胞周期蛋白B1含E盒的最小启动子，这两个基因分别可以响应驱动生物钟和细胞周期的转录振荡器。该比较结果将有助于阐明离散DNA模块如何结合，以响应竞争性调节信号增强或抑制潜在昼夜节律E盒的激活。
