Effects of DNA Superhelical Stress on the Stability of H2B-Ubiquitylated Nucleosomes

Effects of DNA Superhelical Stress on the Stability of H2B-Ubiquitylated Nucleosomes
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DOI:
10.1016/j.jmb.2018.09.014
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发表时间:
2018-12-07
影响因子:
5.6
通讯作者:
Krajewski, Wladyslaw A.
Krajewski, Wladyslaw A.
中科院分区:
生物学2区
文献类型:
--
作者:
Krajewski, Wladyslaw A.

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在核小体水平上,组蛋白翻译后修饰主要作为调节信号发挥作用;此外,一些翻译后修饰可以增强核小体随机折叠,这在“规范”核小体中受到限制。最近,体外研究表明,H2BK34(以及较小程度上的 H2BK120)的对称或不对称核小体泛素化可以破坏核小体 H2A-H2B 二聚体之一的稳定性,并促进核小体转化为六体颗粒 [Krajewski et al. 2017]。 (2018)。核酸研究,46, 7631-7642]。 H2Bub 核小体的这种不稳定性引发了一个问题:它们是否能够适应 DNA 扭转张力的瞬时变化,这种张力几乎是由任何操纵 DNA 链的过程产生的。使用正或负超螺旋 DNA 小环和均质修饰的 H2Bub 组蛋白,我们发现 DNA 拓扑结构可以根据其泛素化状态强烈且选择性地影响核小体稳定性(此处术语“核小体稳定性”是指维持其结构完整性和“规范”核小体动力学特征的核小体特性)。结果表明 H2B 泛素化在放大或减轻 DNA 扭矩对核小体稳定性和动力学的影响方面发挥着作用。 (C) 2018 Elsevier Ltd. 保留所有权利。
On the nucleosome level, histone posttranslational modifications function mainly as the regulatory signals; in addition, some posttranslational modifications can enhance nucleosome stochastic folding, which is restricted in "canonic" nucleosomes. Recently, it has been shown in vitro that symmetric or asymmetric nucleosome ubiquitylation at H2BK34 (and H2BK120, to a lesser extent) can destabilize one of the nucleosomal H2A-H2B dimers and promote nucleosome conversion to a hexasome particle [Krajewski et al. (2018). Nucleic Acids Res., 46, 7631-7642]. Such lability of H2Bub nucleosomes raises a question of whether they could accommodate transient changes in DNA torsional tensions, which are generated by virtually any process that manipulates DNA strands. Using positively or negatively supercoiled DNA minicircles and homogeneously-modified H2Bub histones, we have found that DNA topology could strongly and selectively affect nucleosome stability depending on its ubiquitylation state (here the term "nucleosome stability" means the nucleosome property to maintain its structural integrity and dynamics characteristic to "canonic" nucleosomes). The results point to a role for H2B ubiquitylation in amplifying or mitigating the effects of a DNA torque on the nucleosome stability and dynamics. (C) 2018 Elsevier Ltd. All rights reserved.