The importance of negative superhelicity in inducing the formation of G-quadruplex and i-motif structures in the c-Myc promoter: implications for drug targeting and control of gene expression.
The importance of negative superhelicity in inducing the formation of G-quadruplex and i-motif structures in the c-Myc promoter: implications for drug targeting and control of gene expression.
复制标题
DOI：
10.1021/jm900055s
复制
发表时间：
2009-05-14
影响因子：
7.3
通讯作者：
Hurley LH
中科院分区：
文献类型：
--
作者：
Sun D;Hurley LH
DNA超螺旋在转录调控中的重要性已被发现多年，最近，转录本身已被证明是这种超螺旋的来源。为了模拟转录诱导的负超螺旋效应，将c-Myc启动子中的G-四链体/i-基序形成区掺入超螺旋质粒中。我们表明，使用酶和化学足迹，负超螺旋有利于二级DNA结构在生理条件下的形成。值得注意的是，这些结构与单链DNA模板中形成的结构不同。再加上最近证明的作用，转录诱导的超螺旋在维持一个机械传感器机制，控制发射率的c-Myc启动子，我们提供了一个更完整的图片如何c-Myc转录可能控制。最后，这些生理相关的G-四链体和i-基序结构，沿着与机械传感器机制控制基因表达，提出了新的机制，小分子靶向的转录控制的c-Myc。
The importance of DNA supercoiling in transcriptional regulation has been known for many years, and more recently, transcription itself has been shown to be a source of this superhelicity. To mimic the effect of transcriptionally induced negative superhelicity, the G-quadruplex/i-motif-forming region in the c-Myc promoter was incorporated into a supercoiled plasmid. We show, using enzymatic and chemical footprinting, that negative superhelicity facilitates the formation of secondary DNA structures under physiological conditions. Significantly, these structures are not the same as those formed in single-stranded DNA templates. Together with the recently demonstrated role of transcriptionally induced superhelicity in maintaining a mechanosensor mechanism for controlling the firing rate of the c-Myc promoter, we provide a more complete picture of how c-Myc transcription is likely controlled. Last, these physiologically relevant G-quadruplex and i-motif structures, along with the mechanosensor mechanism for control of gene expression, are proposed as novel mechanisms for small molecule targeting of transcriptional control of c-Myc.
登录
查看更多内容
TrisubStttestated的异丙恶唑作为新的G四链体结合配体：C-KIT癌基因表达的小分子调节。
影响因子：
15
作者：
Bejugam, Mallesham;Sewitz, Sven;Shirude, Pravin S.;Rodriguez, Raphael;Shahid, Ramla;Balasubramanian, Shankar
通讯作者：
Balasubramanian, Shankar
影响因子：
16.8
作者：
Kouzine, Fedor;Sanford, Suzanne;Levens, David
通讯作者：
Levens, David
影响因子：
14.9
作者：
Guo K;Gokhale V;Hurley LH;Sun D
通讯作者：
Sun D
影响因子：
3.1
作者：
Ashley, C;Lee, JS
通讯作者：
Lee, JS
影响因子：
2.9
作者：
Fedoroff, OY;Rangan, A;Hurley, LH
通讯作者：
Hurley, LH