The major G-quadruplex formed in the human BCL-2 proximal promoter adopts a parallel structure with a 13-nt loop in K+ solution.
The major G-quadruplex formed in the human BCL-2 proximal promoter adopts a parallel structure with a 13-nt loop in K+ solution.
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DOI：
10.1021/ja4118945
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发表时间：
2014-02-05
影响因子：
15
通讯作者：
Yang D
中科院分区：
文献类型：
--
作者：
Agrawal P;Lin C;Mathad RI;Carver M;Yang D
人类 BCL-2 基因在 P1 启动子上游含有一个 39 bp 富含 GC 的区域，该区域已被证明与 BCL-2 基因表达的调节至关重要。抑制BCL-2表达可以减少细胞增殖并增强化疗效果。在这里，我们报告了在该 BCL-2 启动子区域的 Pu39 富含 G 的链中形成的主要 G 四链体。 1245G4四联体采用并行结构，具有1个13-nt和两个1-nt链反转环。 1245G4 四联体涉及四个非连续的 G 运行，I、II、IV、V，与之前报道的在中央四个 G 运行上形成的 bcl2 MidG4 四联体不同。出乎意料的是，具有 13-nt 环的平行 1245G4 四联体似乎比混合平行/反平行 MidG4 更稳定。发现具有两个 1-nt 环和一个可变长度中间环的平行链结构在启动子 G-四链体中普遍存在；建议使用可变的中间环来确定特定的整体结构和潜在的配体识别位点。所有四重预测软件都使用 7 nt 的循环长度限制。因此，具有 13-nt 环的 1245G4 四链体的形成和高稳定性具有重要意义。 BCL-2 启动子重叠区域中两个不同的可互换 G 四链体的存在很有趣，这表明基因转录调控和配体调节的新机制。
The human BCL-2 gene contains a 39-bp GC-rich region upstream of the P1 promoter that has been shown to be critically involved in the regulation of BCL-2 gene expression. Inhibition of BCL-2 expression can decrease cellular proliferation and enhance the efficacy of chemotherapy. Here we report the major G-quadruplex formed in the Pu39 G-rich strand in this BCL-2 promoter region. The 1245G4 quadruplex adopts a parallel structure with one 13-nt and two 1-nt chain-reversal loops. The 1245G4 quadruplex involves four nonsuccessive G-runs, I, II, IV, V, unlike the previously reported bcl2 MidG4 quadruplex formed on the central four G-runs. The parallel 1245G4 quadruplex with the 13-nt loop, unexpectedly, appears to be more stable than the mixed parallel/antiparallel MidG4. Parallel-stranded structures with two 1-nt loops and one variable-length middle loop are found to be prevalent in the promoter G-quadruplexes; the variable middle loop is suggested to determine the specific overall structure and potential ligand recognition site. A limit of 7 nt in loop length is used in all quadruplex-predicting software. Thus, the formation and high stability of the 1245G4 quadruplex with a 13-nt loop is significant. The presence of two distinct interchangeable G-quadruplexes in the overlapping region of the BCL-2 promoter is intriguing, suggesting a novel mechanism for gene transcriptional regulation and ligand modulation.