Histone Acetylation Regulates Chromatin Accessibility: Role of H4K16 in Inter-nucleosome Interaction.
Histone Acetylation Regulates Chromatin Accessibility: Role of H4K16 in Inter-nucleosome Interaction.
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DOI：
10.1016/j.bpj.2016.11.015
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发表时间：
2017-02
影响因子：
3.4
通讯作者：
Ruihan Zhang;J. Erler;J. Langowski
中科院分区：
文献类型：
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作者：
Ruihan Zhang;J. Erler;J. Langowski
组蛋白H4的n端尾部是核小体间相互作用不可或缺的介质，这是染色质纤维凝聚所必需的。H4K16乙酰化（H4K16Ac）通过影响染色质结构和与非组蛋白的相互作用来激活基因转录。为了了解H4K16Ac对核小体间相互作用的影响，我们在晶体结构中相邻单位细胞中的两个核小体的背景下对H4尾部进行了模拟研究。采用溶质回火的复片交换法对H4尾部有/没有K16Ac的结合构象进行了取样，并用元动力学方法对自由能格局进行了探讨。结果表明了H4K16的两个重要特征：1)它是将H4尾部锚定在相邻核小体上的第一个按钮；2)它是唯一与酸性斑块相互作用的乙酰化位点。H4K16Ac破坏了K16的静电相互作用，减弱了H4尾部酸性斑块结合，显著增加了H4尾部构象多样性。我们的研究表明，H4K16Ac直接减少了由H4尾部介导的核小体间相互作用，这可能进一步促进非组蛋白在酸性斑块上的结合。
The N-terminal tail of histone H4 is an indispensable mediator for inter-nucleosome interaction, which is required for chromatin fiber condensation. H4K16 acetylation (H4K16Ac) activates gene transcription by influencing both chromatin structure and interplay with nonhistone proteins. To understand the influence of H4K16Ac on inter-nucleosome interaction, we performed a simulation study for the H4 tail in the context of two nucleosomes in neighboring unit cells in the crystal structure. The binding conformation of H4 tail with/without K16Ac was sampled by replica exchange with solute tempering, and the free energy landscape was explored by metadynamics. The results indicate two important features of H4K16: 1) it is the first button to anchor the H4 tail on the adjacent nucleosome; and 2) it is the only acetylation site interacting with the acidic patch. H4K16Ac disrupts the electrostatic interactions of K16, weakens H4 tail-acidic patch binding, and significantly increases H4 tail conformation diversity. Our study suggests that H4K16Ac directly reduces the inter-nucleosome interaction mediated by the H4 tail, which might further encourage the binding of nonhistone proteins on the acidic patch.