Université de Lorraine and CNRS, UMR 7019 LPCT , F-54000 Nancy , France.
Université de Lorraine and CNRS, UMR 7039 CRAN , F-54000 Nancy , France.
J Phys Chem B. 2019 Aug 29;123(34):7365-7371. doi: 10.1021/acs.jpcb.9b05835. Epub 2019 Aug 20.
The behavior of the structural parameters of DNA considering different levels of methylation in CpG islands is studied by means of full-atom molecular dynamics simulations and electronic circular dichroism, both in an artificial model system and in a gene promoter sequence. It is demonstrated that methylation although intrinsically brings quite local perturbations may, if its level is high enough, induce cooperative effects that strongly modify the DNA backbone torsional parameters altering the helicity as compared to the nonmethylated case. Because methylation of the CpG island is correlated with the regulation of gene expression, understanding the structural modifications induced in DNA is crucial to characterize all the fine equilibria into play in epigenetics phenomena.
通过全原子分子动力学模拟和电子圆二色性研究了 CpG 岛不同甲基化水平下 DNA 结构参数的行为，分别在人工模型系统和基因启动子序列中进行了研究。结果表明，尽管甲基化本身会带来相当大的局部扰动，但如果其水平足够高，可能会引起协同效应，这些协同效应会强烈改变 DNA 骨架扭转参数，从而改变与非甲基化情况相比的螺旋结构。由于 CpG 岛的甲基化与基因表达的调控有关，因此了解 DNA 中诱导的结构修饰对于描述表观遗传学现象中所有精细平衡至关重要。
