4n–1 Is a “Sweet Spot” in DNA i-Motif Folding of 2′-Deoxycytidine Homopolymers,Journal of the American Chemical Society

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4n–1 Is a “Sweet Spot” in DNA i-Motif Folding of 2′-Deoxycytidine Homopolymers
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2017-03-21 , DOI: 10.1021/jacs.6b10117
Aaron M. Fleming ₁ , Yun Ding ₁ , R. Aaron Rogers ₁ , Judy Zhu ₁ , Julia Zhu ₁ , Ashlee D. Burton ₁ , Connor B. Carlisle ₁ , Cynthia J. Burrows ₁

Affiliation

Strands of DNA with four or more contiguous runs of 2'-deoxycytidine (dC) nucleotides have the potential to adopt i-motif folds, generally under mildly acidic conditions. Analysis of dC homo-oligonucleotide strands ranging in length from 10 to 30 nucleotides by five different pH-dependent methods identified a pattern in strand length vs stability. Beginning with dC11, which does not fold, the transition pH (pHT) increased with chain length with the addition of up to four nucleotides, after which the stability dramatically decreased, and the trend repeated this cycle up to dC27. The analysis found dCn strands of length 15, 19, 23, and 27 nucleotides (i.e., 4n-1) to have pHT values >7.2 and thermal stabilities >37 °C at pH 7.0. Model studies using thymidine nucleotides to lock in i-motif loop lengths support the conclusion that the most stable dCn i-motifs possess one nucleotide in each of the three loops and a core built of an even number of base pairs. The pattern identified from the model studies occurs with a frequency of four nucleotides at lengths of 15, 19, 23, and 27 in accordance with the results obtained for the dCn strands. This observation led us to interrogate the human genome for dCn runs. Inspection of the human genome indicates that dCn runs are enriched in critical regions of the genome (promoters, UTRs, and introns), while being depleted in coding and intergenic regions, and these findings may have biological implications. Lastly, the ability to tune i-motif stabilities by the length of the strand might be harnessed for stimulus-responsive applications in DNA scaffolds, sensors, nanotechnology, and other chemical applications.

中文翻译：

4n-1 是 2'-脱氧胞苷均聚物的 DNA i-Motif 折叠的“甜蜜点”

通常在弱酸性条件下，具有四个或更多 2'-脱氧胞苷 (dC) 核苷酸连续运行的 DNA 链有可能采用 i-基序折叠。通过五种不同的 pH 依赖性方法对长度为 10 到 30 个核苷酸的 dC 同源寡核苷酸链进行分析，确定了链长度与稳定性的模式。从不折叠的 dC11 开始，过渡 pH (pHT) 随着链长的增加而增加，添加多达四个核苷酸，之后稳定性急剧下降，并且该趋势重复该循环直至 dC27。分析发现，长度为 15、19、23 和 27 个核苷酸（即 4n-1）的 dCn 链在 pH 7.0 时具有 >7.2 的 pHT 值和 >37 °C 的热稳定性。使用胸苷核苷酸锁定 i-motif 环长度的模型研究支持以下结论：最稳定的 dCn i-motifs 在三个环中的每一个中都拥有一个核苷酸，并且核心由偶数个碱基对构成。根据对 dCn 链获得的结果，从模型研究中确定的模式以 4 个核苷酸的频率出现，长度为 15、19、23 和 27。这一观察导致我们询问人类基因组以进行 dCn 运行。对人类基因组的检查表明 dCn 运行在基因组的关键区域（启动子、UTR 和内含子）中富集，而在编码和基因间区域中却被耗尽，这些发现可能具有生物学意义。最后，

更新日期：2017-03-21

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