Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa, Sakyo 606-8502, Kyoto Japan.
Sci Rep. 2016 Oct 4;6:34441. doi: 10.1038/srep34441.
Histone tail acetylation is a key epigenetic marker that tends to open chromatin folding and activate transcription. Despite intensive studies, precise roles of individual lysine acetylation in chromatin folding have only been poorly understood. Here, we revealed structural dynamics of tri-nucleosomes with several histone tail acetylation states and analyzed histone tail interactions with DNA by performing molecular simulations at an unprecedentedly high resolution. We found versatile acetylation-dependent landscapes of tri-nucleosome. The H4 and H2A tail acetylation reduced the contact between the first and third nucleosomes mediated by the histone tails. The H3 tail acetylation reduced its interaction with neighboring linker DNAs resulting in increase of the distance between consecutive nucleosomes. Notably, two copies of the same histone in a single nucleosome have markedly asymmetric interactions with DNAs, suggesting specific pattern of nucleosome docking albeit high inherent flexibility. Estimated transcription factor accessibility was significantly high for the H4 tail acetylated structures.
组蛋白尾部乙酰化是一种关键的表观遗传标记，往往能打开染色质折叠并激活转录。尽管进行了深入研究，但个别赖氨酸乙酰化在染色质折叠中的精确作用仍知之甚少。在这里，我们通过在前所未有的高分辨率下进行分子模拟，揭示了具有几种组蛋白尾部乙酰化状态的三聚体核小体的结构动力学，并分析了组蛋白尾部与 DNA 的相互作用。我们发现了三聚体核小体的多种依赖于乙酰化的图谱。H4 和 H2A 尾部的乙酰化减少了由组蛋白尾部介导的第一个和第三个核小体之间的接触。H3 尾部的乙酰化减少了它与相邻连接 DNA 的相互作用，导致连续核小体之间的距离增加。值得注意的是，在单个核小体中，相同组蛋白的两个拷贝与 DNA 具有明显不对称的相互作用，这表明尽管具有很高的固有灵活性，但存在特定的核小体对接模式。对于 H4 尾部乙酰化结构，估计转录因子的可及性显著提高。
