Elucidation of the mechanism of nucleosomal structural change mediated by histone modifications

阐明组蛋白修饰介导的核小体结构变化机制

• 批准号: 21370052
• 负责人: HORIKOSHI Masami
• 金额: $ 12.15万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21370052/
• 关键词: 遺伝子の情報発現と複製; 遺伝子; 酵素; 生体分子; 構造変換; 蛋白質; 発現制御

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. We determined at 3.3 A 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 in this study is the initial structure-based model of the biological signaling fromhistone modifications to structural change of the nucleosome (hi-MOST model).

启动子区域周围的核小体被分解以响应各种信号（例如组蛋白的乙酰化和甲基化）进行转录。虽然组蛋白乙酰化识别布罗莫结构域和参与核小体解体的因子之间的相互作用已被报道，但尚未获得连接组蛋白修饰和核小体解体的结构基础。我们在3.3 A分辨率下测定了组蛋白伴侣细胞周期基因1（CCG 1）相互作用因子A/抗沉默功能1（CIA/ASF 1）与转录因子IID的CCG 1/TAF 1/TAF（II）250亚基中的双溴结构域复合物的晶体结构。结构，生化和生物学研究表明，双溴结构域和CIA/ASF 1之间的相互作用是必需的共定位，组蛋白驱逐，和pol II进入活性启动子区域。此外，本晶体结构具有可以连接组蛋白乙酰化和CIA/ASF 1介导的组蛋白驱逐的特征。这些发现表明CIA/ASF 1和双布罗莫结构域之间的分子复合物在活性启动子区域的位点特异性组蛋白驱逐中起关键作用。本研究提出的模型是从组蛋白修饰到核小体结构改变的生物信号传递的初始模型（hi-MOST模型）。

项目成果

Network-based histone "modification web" theory and "DESS" strategy for elucidating the physiological significance of histone modifications.

基于网络的组蛋白“修饰网”理论和“DESS”策略阐明了组蛋白修饰的生理意义。

• 发表时间: 2011
• 作者: Hayashi Y;Horikoshi M
• 通讯作者: Horikoshi M

Global analysis of mutual interaction surfaces of nucleosomes with comprehensive point mutants

• DOI: 10.1111/j.1365-2443.2009.01350.x
• 发表时间: 2009-11
• 期刊: Genes to Cells
• 影响因子: 2.1
• 作者: M. Sakamoto;Shuhei Noguchi;S. Kawashima;Yusuke Okada;T. Enomoto;M. Seki;M. Horikoshi

Chromatin dynamics mediated by histone modifiers and histone chaperones in postreplicative recombination

• DOI: 10.1111/j.1365-2443.2010.01435.x
• 发表时间: 2010-09-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Endo, Hirohito;Kawashima, Satoshi;Horikoshi, Masami
• 通讯作者: Horikoshi, Masami

スーパーサイエンスハイスクール講義-LET IT BE OR NOT

超级科学高中讲座-无论是还是不

• 发表时间: 2009
• 作者: 東森生;田中爾織;水澤寛太;内山実;高橋明義;斎藤裕見子;塩田清二;松田恒平;堀越正美
• 通讯作者: 堀越正美

Theoretical framework for the histone modification network: modifications in the unstructured histone tails form a robust scale-free network

• DOI: 10.1111/j.1365-2443.2009.01314.x
• 发表时间: 2009-07-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Hayashi, Yohei;Senda, Toshiya;Horikoshi, Masami
• 通讯作者: Horikoshi, Masami