Theoretical framework for the histone modification network: modifications in the unstructured histone tails form a robust scale-free network
Theoretical framework for the histone modification network: modifications in the unstructured histone tails form a robust scale-free network
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DOI：
10.1111/j.1365-2443.2009.01314.x
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发表时间：
2009-07-01
期刊：
影响因子：
2.1
通讯作者：
Horikoshi, Masami
中科院分区：
文献类型：
--
作者：
Hayashi, Yohei;Senda, Toshiya;Horikoshi, Masami
对组蛋白修饰及其在细胞核中后续反应之间关系的研究迅速增加，揭示了组蛋白修饰系统是复杂的，对点突变具有很强的抵抗力。流行的理论框架(组蛋白密码假说)不足以解释复杂性或稳健性，这使得制定一个新的理论框架既必要又可取。在这里，我们建立了一个组蛋白修饰调控网络的模型，其中我们将组蛋白修饰编码为节点，将组蛋白修饰之间的调控相互作用编码为链接。该网络具有无标度特性和具有伪镜对称结构的子网络结构，这支持了组蛋白修饰网络的健壮性。此外，我们还证明了组蛋白的非结构尾部区域适合于获得这种无标度性质。我们的模型和相关见解为组蛋白修饰网络系统的整体架构提供了第一个框架，特别是关于非结构化组蛋白尾部区域的结构和功能角色。一般来说，天然展开区域(蛋白质)的翻译后“修饰网”可以作为信号路由器，对大量信号信息进行稳健的处理。
A rapid increase in research on the relationship between histone modifications and their subsequent reactions in the nucleus has revealed that the histone modification system is complex, and robust against point mutations. The prevailing theoretical framework (the histone code hypothesis) is inadequate to explain either the complexity or robustness, making the formulation of a new theoretical framework both necessary and desirable. Here, we develop a model of the regulatory network of histone modifications in which we encode histone modifications as nodes and regulatory interactions between histone modifications as links. This network has scale-free properties and subnetworks with a pseudo-mirror symmetry structure, which supports the robustness of the histone modification network. In addition, we show that the unstructured tail regions of histones are suitable for the acquisition of this scale-free property. Our model and related insights provide the first framework for an overall architecture of a histone modification network system, particularly with regard to the structural and functional roles of the unstructured histone tail region. In general, the post-translational "modification webs" of natively unfolded regions (proteins) may function as signal routers for the robust processing of the large amounts of signaling information.