Molecular Biology Institute of Barcelona (IBMB), Spanish National Research Council (CSIC), Barcelona, 08028, Spain.
Nat Commun. 2018 Sep 28;9(1):3989. doi: 10.1038/s41467-018-06547-w.
The interplay between chromatin structure and DNA topology is a fundamental, yet elusive, regulator of genome activities. A paradigmatic case is the "linking number paradox" of nucleosomal DNA, which refers to the incongruence between the near two left-handed superhelical turns of DNA around the histone octamer and the DNA linking number difference (∆Lk) stabilized by individual nucleosomes, which has been experimentally estimated to be about -1.0. Here, we analyze the DNA topology of a library of mononucleosomes inserted into small circular minichromosomes to determine the average ∆Lk restrained by individual nucleosomes in vivo. Our results indicate that most nucleosomes stabilize about -1.26 units of ∆Lk. This value balances the twist (∆Tw ≈ + 0.2) and writhe (∆Wr ≈ -1.5) deformations of nucleosomal DNA in terms of the equation ∆Lk = ∆Tw + ∆Wr. Our finding reconciles the existing discrepancy between theoretical and observed measurement of the ΔLk constrained by nucleosomes.
染色质结构和 DNA 拓扑之间的相互作用是调节基因组活性的基本但难以捉摸的因素。核小体 DNA 的“连接数悖论”就是一个典型的例子，它指的是组蛋白八聚体周围 DNA 的近两个左旋超螺旋与单个核小体稳定的 DNA 连接数差异（∆Lk）之间的不一致，实验估计该差异约为-1.0。在这里，我们分析了插入到小圆形迷你染色体中的单核小体文库的 DNA 拓扑结构，以确定体内单个核小体限制的平均∆Lk。我们的结果表明，大多数核小体稳定的∆Lk 值约为-1.26 个单位。根据公式∆Lk=∆Tw+∆Wr，该值平衡了核小体 DNA 的扭曲（∆Tw≈+0.2）和纽结（∆Wr≈-1.5）变形。我们的发现调和了核小体限制的∆Lk 的理论和观测测量之间现有的差异。
