Role of Extrachromosomal Histone H2B on Recognition of DNA Viruses and Cell Damage.
Role of Extrachromosomal Histone H2B on Recognition of DNA Viruses and Cell Damage.
复制标题
DOI：
10.3389/fgene.2013.00091
复制
发表时间：
2013
影响因子：
3.7
通讯作者：
Suzuki K
中科院分区：
文献类型：
--
作者：
Kobiyama K;Kawashima A;Jounai N;Takeshita F;Ishii KJ;Ito T;Suzuki K
组蛋白是染色质结构的重要组成部分，组蛋白修饰在转录、基因沉默和免疫等多种细胞功能中发挥着重要作用。组蛋白在染色体外环境中也发挥着独特的作用。染色体外组蛋白 H2B 充当胞质传感器，检测源自感染因子或受损细胞的双链 DNA (dsDNA) 片段，以激活各种细胞类型的先天性和获得性免疫反应。它还通过 COOH 末端导入组织组蛋白 H2B 和 IPS-1 (CIAO) 的 9 相关衔接子与干扰素 (IFN)-β 启动子刺激子 1 (IPS-1)（一种激活先天免疫的重要衔接子分子）发生物理相互作用，产生独特的信号复合物，诱导 dsDNA 诱导的 I 型 IFN 产生。这种分子平台充当细胞传感器，在病毒感染和细胞损伤的情况下识别异常的 dsDNA。这种机制也可能在自身免疫、移植排斥、基因介导的疫苗和其他治疗应用中发挥作用。
Histones are essential components of chromatin structure, and histone modification plays an important role in various cellular functions including transcription, gene silencing, and immunity. Histones also play distinct roles in extrachromosomal settings. Extrachromosomal histone H2B acts as a cytosolic sensor to detect double-stranded DNA (dsDNA) fragments derived from infectious agents or damaged cells to activate innate and acquired immune responses in various cell types. It also physically interacts with interferon (IFN)-β promoter stimulator 1 (IPS-1), an essential adaptor molecule that activates innate immunity, through COOH-terminal importin 9-related adaptor organizing histone H2B and IPS-1 (CIAO), resulting in a distinct signaling complex that induces dsDNA-induced type I IFN production. Such a molecular platform acts as a cellular sensor to recognize aberrant dsDNA in cases of viral infection and cell damage. This mechanism may also play roles in autoimmunity, transplantation rejection, gene-mediated vaccines, and other therapeutic applications.