I-Motif Structures Formed in the Human c-MYC Promoter Are Highly Dynamic-Insights into Sequence Redundancy and I-Motif Stability
I-Motif Structures Formed in the Human c-MYC Promoter Are Highly Dynamic-Insights into Sequence Redundancy and I-Motif Stability
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DOI：
10.1371/journal.pone.0011647
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发表时间：
2010-07-19
期刊：
影响因子：
3.7
通讯作者：
Yang, Danzhou
中科院分区：
文献类型：
--
作者：
Dai, Jixun;Hatzakis, Emmanuel;Yang, Danzhou
c-MYC启动子的富含GC的核酸酶超敏元件III 1（NHE III 1）在很大程度上控制着c-MYC癌基因的转录活性。该区域的富C链可以形成I基序DNA二级结构。我们确定了在NHE III 1中形成的主要I基序的折叠模式，其可以在近中性pH下形成。虽然我们发现在胞嘧啶的四个3'连续运行中形成的I基序似乎是最有利的，但我们的结果表明，c-MYC NHE III 1的富含C的链表现出高度的动态平衡。使用这个区域的三取代低聚物，我们确定了两个平衡环异构体的形成，其中之一包含翻转的胞嘧啶。我们的研究结果表明，插入胞嘧啶（+）-胞嘧啶碱基对并不总是必要的分子内的I-基序。c-MYC I基序的动态特征是NHE III 1序列固有的，似乎为c-MYC I基序提供了稳定性。
The GC-rich nuclease hypersensitivity element III1 (NHE III1) of the c-MYC promoter largely controls the transcriptional activity of the c-MYC oncogene. The C-rich strand in this region can form I-motif DNA secondary structures. We determined the folding pattern of the major I-motif formed in the NHE III1, which can be formed at near-neutral pH. While we find that the I-motif formed in the four 3' consecutive runs of cytosines appears to be the most favored, our results demonstrate that the C-rich strand of the c-MYC NHE III1 exhibits a high degree of dynamic equilibration. Using a trisubstituted oligomer of this region, we determined the formation of two equilibrating loop isomers, one of which contains a flipped-out cytosine. Our results indicate that the intercalative cytosine(+)-cytosine base pairs are not always necessary for an intramolecular I-motif. The dynamic character of the c-MYC I-motif is intrinsic to the NHE III1 sequence and appears to provide stability to the c-MYC I-motif.