Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling
Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling
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DOI：
10.3389/fmolb.2019.00133
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发表时间：
2019-11-28
影响因子：
5
通讯作者：
Togashi, Yuichi
中科院分区：
文献类型：
--
作者：
Kameda, Takeru;Awazu, Akinori;Togashi, Yuichi
核小体是染色体的结构单位，由包裹在组蛋白周围的DNA组成，在染色质结构的致密化和调节中起重要作用。虽然规范核小体的结构和动力学已经被广泛研究，但当它们的结构或位置被调制时，处于中间状态的核小体的结构和动力学却很少被理解。特别是，部分解体的核小体的动力学特征在以前的研究中没有讨论过。利用全原子分子动力学模拟，在这项研究中，我们研究了缺乏组蛋白二聚体的核小体结构的动力学和稳定性。缺乏组蛋白H2 A/H2 B二聚体的核小体中的DNA由于DNA和组蛋白之间的局部相互作用的丧失而急剧变形。相比之下，缺乏H3/H4的核小体中的DNA构象与典型核小体相似，因为H2 A C-末端结构域渗透了最初由解离的H3/H4组蛋白占据的空间，并限制了DNA动力学。我们的研究结果表明，除了组蛋白伴侣，核小体的内在动力学支持H2 A/H2 B的交换，这是显着更频繁的H3/H4。
Nucleosomes are structural units of the chromosome consisting of DNA wrapped around histone proteins, and play important roles in compaction and regulation of the chromatin structure. While the structure and dynamics of canonical nucleosomes have been studied extensively, those of nucleosomes in intermediate states, that occur when their structure or positioning is modulated, have been less understood. In particular, the dynamic features of partially disassembled nucleosomes have not been discussed in previous studies. Using all-atom molecular dynamics simulations, in this study, we investigated the dynamics and stability of nucleosome structures lacking a histone-dimer. DNA in nucleosomes lacking a histone H2A/H2B dimer was drastically deformed due to loss of local interactions between DNA and histones. In contrast, conformation of DNA in nucleosomes lacking H3/H4 was similar to the canonical nucleosome, as the H2A C-terminal domain infiltrated the space originally occupied by the dissociated H3/H4 histones and restricted DNA dynamics in close proximity. Our results suggest that, besides histone chaperones, the intrinsic dynamics of nucleosomes support the exchange of H2A/H2B, which is significantly more frequent than that of H3/H4.