Secondary structures of the core histone N-terminal tails: their role in regulating chromatin structure.
Secondary structures of the core histone N-terminal tails: their role in regulating chromatin structure.
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DOI：
10.1007/978-94-007-4525-4_2
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发表时间：
2013-01-01
影响因子：
--
通讯作者：
Patterton, Hugh-G
中科院分区：
文献类型：
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作者：
du Preez, Louis L;Patterton, Hugh-G
在中等盐浓度下，核心组蛋白 N 末端尾部从其在核小体中的结合位置解离，并且在晶体中呈现非结构化。这表明尾巴对染色质结构的贡献微乎其微。然而，体外研究表明，尾部参与一系列核小体内和核小体间以及纤维间的接触。 H4 尾对于染色质压缩至关重要，它与晶体中相邻的核小体接触。 H4K16 的乙酰化会消除核小体阵列折叠成 30 nm 纤维的能力。二级结构预测软件的应用表明组蛋白尾部存在扩展的结构区域。分子动力学研究进一步表明，H3 和 H4 尾部的部分假定 α 螺旋和 β 链含量因 DNA 的存在而增强，并且尾部的翻译后修饰对这些结构具有重大影响。圆二色性和 NMR 显示 H3 和 H4 尾部表现出显着的 α 螺旋含量，该含量通过尾部乙酰化而增加。因此，来自生物物理和计算方法的有力证据表明，核心组蛋白尾部，特别是 H3 和 H4 的尾部，是结构化的，并且这些结构受到翻译后修饰的影响。本章综述了核心组蛋白尾部的位置、结合位点和二级结构的研究，并讨论了组蛋白尾部结构在染色质组织调节中的可能作用及其对人类疾病的影响。
The core histone N-terminal tails dissociate from their binding positions in nucleosomes at moderate salt concentrations, and appear unstructured in the crystal. This suggested that the tails contributed minimally to chromatin structure. However, in vitro studies have shown that the tails were involved in a range of intra- and inter-nucleosomal as well as inter-fibre contacts. The H4 tail, which is essential for chromatin compaction, was shown to contact an adjacent nucleosome in the crystal. Acetylation of H4K16 was shown to abolish the ability of a nucleosome array to fold into a 30 nm fibre. The application of secondary structure prediction software has suggested the presence of extended structured regions in the histone tails. Molecular Dynamics studies have further shown that sections of the H3 and H4 tails assumed alpha-helical and beta-strand content that was enhanced by the presence of DNA, and that post-translational modifications of the tails had a major impact on these structures. Circular dichroism and NMR showed that the H3 and H4 tails exhibited significant alpha-helical content, that was increased by acetylation of the tail. There is thus strong evidence, both from biophysical and from computational approaches, that the core histones tails, particularly that of H3 and H4, are structured, and that these structures are influenced by post-translational modifications. This chapter reviews studies on the position, binding sites and secondary structures of the core histone tails, and discusses the possible role of the histone tail structures in the regulation of chromatin organization, and its impact on human disease.