Probing the Ionic Atmosphere and Hydration of the c-MYC i-motif,Journal of the American Chemical Society

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Probing the Ionic Atmosphere and Hydration of the c-MYC i-motif
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2018-02-02 , DOI: 10.1021/jacs.7b11537
Lutan Liu ₁ , Byul G. Kim ₁ , Ujala Feroze ₁ , Robert B. Macgregor ₁ , Tigran V. Chalikian ₁

Affiliation

G-quadruplexes and i-motifs are noncanonical secondary structures of DNA that appear to play a number of regulatory roles in the genome with clear connection to disease. Characterization of the forces stabilizing these structures is necessary for developing an ability to induce G-quadruplex and/or i-motif structures at selected genomic loci in a controlled manner. We report here the results of pH-dependent acoustic and densimetric measurements and UV melting experiments at elevated pressures to scrutinize changes in hydration and ionic atmosphere accompanying i-motif formation by the C-rich DNA sequence from the promoter region of the human c-MYC oncogene [5'-d(TTACCCACCCTACCCACCCTCA)] (ODN). We also conducted pH-dependent acoustic and densimetric characterizations of two DNA molecules that are compositionally identical to ODN but do not adopt the i-motif conformation, 5'-d(CTCTCACCACACCACACCTCTC) (ODN1) and 5'-d(CACACTCCTCACCTCTCCACAC) (ODN2). Our results reveal that i-motif formation by ODN is not accompanied by changes in volume and compressibility. The volumetric similarity of the i-motif and coil states of ODN implies a fortuitous compensation between changes in the intrinsic and hydration contributions to volume and compressibility. Analysis of the pH-dependent volumetric profiles of ODN, ODN1, and ODN2, along with the data on volumetric changes accompanying the protonation of isolated cytosine and deoxycytidine, suggests that protonation of the cytosines in the oligonucleotides causes release of the majority if not all of their counterions to the bulk. Thus, in the i-motif conformation, the oligomer no longer acts as a polyelectrolyte insofar as counterions are concerned. We discuss the biological ramifications of our results.

中文翻译：

探索 c-MYC i-motif 的离子气氛和水合作用

G-四链体和 i-motifs 是 DNA 的非规范二级结构，它们似乎在基因组中发挥了许多调节作用，与疾病有明确的联系。稳定这些结构的力的表征对于开发以受控方式在选定基因组位点诱导 G-四链体和/或 i-基序结构的能力是必要的。我们在此报告了在升高的压力下进行的 pH 依赖性声学和密度测量以及 UV 熔解实验的结果，以检查人类 c-MYC 启动子区域的富含 C 的 DNA 序列伴随 i-motif 形成的水合作用和离子气氛的变化癌基因 [5'-d(TTACCCACCCTACCCACCCTCA)] (ODN)。我们还对组成与 ODN 相同但不采用 i-motif 构象的两个 DNA 分子进行了 pH 依赖性声学和密度表征，5'-d(CTCTCACCACACCACACCTCTC) (ODN1) 和 5'-d(CACACTCCTCACCTCTCCCACAC) (ODN2 ）。我们的结果表明，ODN 形成的 i-motif 不伴随体积和可压缩性的变化。ODN 的 i-motif 和线圈状态的体积相似性意味着内在和水合对体积和可压缩性的贡献变化之间的偶然补偿。分析 ODN、ODN1 和 ODN2 的 pH 依赖性体积分布，以及伴随分离的胞嘧啶和脱氧胞苷质子化的体积变化数据，表明寡核苷酸中胞嘧啶的质子化导致大部分（如果不是全部）抗衡离子释放到主体中。因此，在 i-motif 构象中，就抗衡离子而言，低聚物不再充当聚电解质。我们讨论了我们结果的生物学后果。

更新日期：2018-02-02

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