Flexible histone tails in a new mesoscopic oligonucleosome model
Flexible histone tails in a new mesoscopic oligonucleosome model
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DOI：
10.1529/biophysj.106.083006
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发表时间：
2006-07-01
影响因子：
3.4
通讯作者：
Schlick, Tamar
中科院分区：
文献类型：
--
作者：
Arya, Gaurav;Zhang, Qing;Schlick, Tamar
我们描述了一个新的介观模型的oligonucleosomes，采用灵活的组蛋白尾巴。使用离散表面电荷优化模型对核小体核心进行建模，该模型将核小体视为由数百个点电荷表示的静电表面;使用离散弹性链模型处理接头DNA;使用珠/链流体动力学方法将组蛋白尾部建模为连接珠的链，其中每个珠代表五个蛋白残基。适当的电荷和力场被分配给每个组蛋白链，以便在不同的盐条件下再现相应的原子组蛋白尾部的静电势、结构和动力学。在不同的大小和不同的盐浓度所产生的oligonucleosomes的动力学模拟布朗动力学与完整的流体动力学相互作用。分析表明，新的介观模型再现实验结果比它的前辈，其中模拟组蛋白尾部作为刚性实体。特别是，我们的模型与灵活的组蛋白尾巴：正确地占盐依赖的构象变化的组蛋白尾巴;产生实验获得的值组蛋白尾巴介导的核心/核心吸引力的能量;并认为部分屏蔽的DNA连接器之间的静电排斥的结果组蛋白尾巴的空间分布。这些效应对于调节染色质结构至关重要，但在具有刚性组蛋白尾部的模型中不存在或处理不当。这种寡核小体模型的发展为研究组蛋白尾部及其变体通过调节染色质结构介导基因表达的作用开辟了新的途径。
We describe a new mesoscopic model of oligonucleosomes that incorporates flexible histone tails. The nucleosome cores are modeled using the discrete surface-charge optimization model, which treats the nucleosome as an electrostatic surface represented by hundreds of point charges; the linker DNAs are treated using a discrete elastic chain model; and the histone tails are modeled using a bead/chain hydrodynamic approach as chains of connected beads where each bead represents five protein residues. Appropriate charges and force fields are assigned to each histone chain so as to reproduce the electrostatic potential, structure, and dynamics of the corresponding atomistic histone tails at different salt conditions. The dynamics of resulting oligonucleosomes at different sizes and varying salt concentrations are simulated by Brownian dynamics with complete hydrodynamic interactions. The analyses demonstrate that the new mesoscopic model reproduces experimental results better than its predecessors, which modeled histone tails as rigid entities. In particular, our model with flexible histone tails: correctly accounts for salt-dependent conformational changes in the histone tails; yields the experimentally obtained values of histone-tail mediated core/core attraction energies; and considers the partial shielding of electrostatic repulsion between DNA linkers as a result of the spatial distribution of histone tails. These effects are crucial for regulating chromatin structure but are absent or improperly treated in models with rigid histone tails. The development of this model of oligonucleosomes thus opens new avenues for studying the role of histone tails and their variants in mediating gene expression through modulation of chromatin structure.