Intramolecularly folded G-quadruplex and i-motif structures in the proximal promoter of the vascular endothelial growth factor gene.
Intramolecularly folded G-quadruplex and i-motif structures in the proximal promoter of the vascular endothelial growth factor gene.
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DOI：
10.1093/nar/gkn380
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发表时间：
2008-08
影响因子：
14.9
通讯作者：
Sun D
中科院分区：
文献类型：
--
作者：
Guo K;Gokhale V;Hurley LH;Sun D
血管内皮生长因子（VEGF）基因近端启动子的多聚鸟嘌呤/多聚胞嘧啶（polyG/polyC）区对转录激活至关重要。富含鸟嘌呤（G-丰富）和胞嘧啶（C-丰富）链上的这道被证明形成特定的二级结构，其特征在于G-四链体和i-基序，分别。结合硫酸二甲酯（DMS）足迹，聚合酶终止试验和圆二色性（CD）光谱的G-丰富的链的突变分析表明，G-四链体含有1：4：1的双链反转环是最稳定的构象，这条链很容易采用。这些研究提供了强有力的证据，环区的大小在确定G-四链体的最有利的折叠模式中起着关键作用。还通过突变分析结合Br 2足迹法和CD光谱法确定了互补富含C链上形成的二级结构。我们的研究结果表明，在pH值为5.9，这条链是能够形成一个分子内的i-基序结构，涉及6个C-C+碱基对和2：3：2环的配置。总之，我们的结果表明，G-四链体和i-基序结构能够形成的G-和C-丰富的链，分别在VEGF近端启动子的polyG/polyC道的条件下，有利于从B-DNA的过渡到非B-DNA构象。
A polyguanine/polycytosine (polyG/polyC) tract in the proximal promoter of the vascular endothelial growth factor (VEGF) gene is essential for transcriptional activation. The guanine-rich (G-rich) and cytosine-rich (C-rich) strands on this tract are shown to form specific secondary structures, characterized as G-quadruplexes and i-motifs, respectively. Mutational analysis of the G-rich strand combined with dimethyl sulfate (DMS) footprinting, a polymerase stop assay, and circular dichroism (CD) spectroscopy revealed that the G-quadruplex containing a 1:4:1 double-chain reversal loop is the most thermodynamically stable conformation that this strand readily adopts. These studies provide strong evidence that the size of loop regions plays a critical role in determining the most favored folding pattern of a G-quadruplex. The secondary structure formed on the complementary C-rich strand was also determined by mutational analysis combined with Br2 footprinting and CD spectroscopy. Our results reveal that at a pH of 5.9 this strand is able to form an intramolecular i-motif structure that involves six C–C+ base pairs and a 2:3:2 loop configuration. Taken together, our results demonstrate that the G-quadruplex and i-motif structures are able to form on the G- and C-rich strands, respectively, of the polyG/polyC tract in the VEGF proximal promoter under conditions that favor the transition from B-DNA to non-B-DNA conformations.
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影响因子：
5.3
作者：
Michelotti, EF;Michelotti, GA;Levens, D
通讯作者：
Levens, D
DOI：
10.1038/nsb0294-83
发表时间：
1994-02-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
AHMED, S;KINTANAR, A;HENDERSON, E
通讯作者：
HENDERSON, E
影响因子：
4.8
作者：
GRUGEL, S;FINKENZELLER, G;MARME, D
通讯作者：
MARME, D
影响因子：
4.8
作者：
LI, J;PERRELLA, MA;LEE, ME
通讯作者：
LEE, ME
影响因子：
15
作者：
Dexheimer, TS;Sun, D;Hurley, LH
通讯作者：
Hurley, LH