Structure of the histone chaperone CIA/ASF1-double bromodomain complex linking histone modifications and site-specific histone eviction
Structure of the histone chaperone CIA/ASF1-double bromodomain complex linking histone modifications and site-specific histone eviction
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DOI：
10.1073/pnas.0912509107
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发表时间：
2010-05-04
影响因子：
11.1
通讯作者：
Horikoshi, Masami
中科院分区：
文献类型：
--
作者：
Akai, Yusuke;Adachi, Naruhiko;Horikoshi, Masami
启动子区域周围的核小体被分解以进行转录，以响应各种信号，如组蛋白的乙酰化和甲基化。尽管组蛋白乙酰化识别溴域与核小体解体相关因子之间的相互作用已有报道，但尚未获得组蛋白修饰与核小体解体之间的结构基础。在此，我们在3.3埃分辨率下确定了组蛋白伴侣细胞周期基因1(CCG1)与转录因子IID的CCG1/TAF1/TAF(II)250亚基中的双溴结构域相互作用因子A/抗沉默功能1(CIA/ASF1)的晶体结构。结构、生化和生物学研究表明，双溴结构域与CIA/ASF1之间的相互作用对于它们的共定位、组蛋白驱逐和PolII进入活性启动子区域是必需的。此外，目前的晶体结构特征可以连接组蛋白乙酰化和CIA/ASF1介导组蛋白驱逐。这些发现表明CIA/ASF1与双溴结构域之间的分子复合体在活性启动子区域的特异性组蛋白驱逐中起着关键作用。我们在这里提出的模型是从组蛋白修饰到核小体结构变化的生物信号传递的初始基于结构的模型(HI-Most模型)。
Nucleosomes around the promoter region are disassembled for transcription in response to various signals, such as acetylation and methylation of histones. Although the interactions between histone-acetylation-recognizing bromodomains and factors involved in nucleosome disassembly have been reported, no structural basis connecting histone modifications and nucleosome disassembly has been obtained. Here, we determined at 3.3 angstrom resolution the crystal structure of histone chaperone cell cycle gene 1 (CCG1) interacting factor A/antisilencing function 1 (CIA/ASF1) in complex with the double bromodomain in the CCG1/TAF1/TAF(II)250 subunit of transcription factor IID. Structural, biochemical, and biological studies suggested that interaction between double bromodomain and CIA/ASF1 is required for their colocalization, histone eviction, and pol II entry at active promoter regions. Furthermore, the present crystal structure has characteristics that can connect histone acetylation and CIA/ASF1-mediated histone eviction. These findings suggest that the molecular complex between CIA/ASF1 and the double bromodomain plays a key role in site-specific histone eviction at active promoter regions. The model we propose here is the initial structure-based model of the biological signaling from histone modifications to structural change of the nucleosome (hi-MOST model).