"Direct" and "Indirect" Effects of Histone Modifications: Modulation of Sterical Bulk as a Novel Source of Functionality
"Direct" and "Indirect" Effects of Histone Modifications: Modulation of Sterical Bulk as a Novel Source of Functionality
复制标题
DOI：
10.1002/bies.201900136
复制
发表时间：
2019-12-05
期刊：
影响因子：
4
通讯作者：
Krajewski, Wladyslaw A.
中科院分区：
文献类型：
--
作者：
Krajewski, Wladyslaw A.
讨论了组蛋白翻译后修饰（PTMs）的染色质调控原理，重点讨论了由于泛素和SUMO等大体积组蛋白修饰施加的空间和机械限制而导致的染色质功能状态的潜在改变。在经典观点中，PTMs作为组蛋白“读取器”的招募平台和染色质阵列压缩的决定因素。通过“小”化学修饰（如乙酰化、磷酸化）改变组蛋白电荷可以调节核小体的自发动力学，而不会影响核小体的整体结构。染色质加工机制可以利用核小体包裹中的这些波动。相比之下，泛素和SUMO在大小上与组蛋白相当，这些PTMs可能与典型核小体组织相冲突似乎是合乎逻辑的。提出了一个实验可验证的假设，即通过增加空间体积，这些PTMs可以强有力地改变核小体的初级结构。这里提出的模型强调了组蛋白PTMs调节染色质动力学、初级结构和功能的机制多样性。
The chromatin-regulatory principles of histone post-translational modifications (PTMs) are discussed with a focus on the potential alterations in chromatin functional state due to steric and mechanical constraints imposed by bulky histone modifications such as ubiquitin and SUMO. In the classical view, PTMs operate as recruitment platforms for histone "readers," and as determinants of chromatin array compaction. Alterations of histone charges by "small" chemical modifications (e.g., acetylation, phosphorylation) could regulate nucleosome spontaneous dynamics without globally affecting nucleosome structure. These fluctuations in nucleosome wrapping can be exploited by chromatin-processing machinery. In contrast, ubiquitin and SUMO are comparable in size to histones, and it seems logical that these PTMs could conflict with canonical nucleosome organization. An experimentally testable hypothesis that by adding sterical bulk these PTMs can robustly alter nucleosome primary structure is proposed. The model presented here stresses the diversity of mechanisms by which histone PTMs regulate chromatin dynamics, primary structure and, hence, functionality.