• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4
【24h】

Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4

机译：组蛋白伴侣CIA / ASF1与组蛋白H3和H4复合的结构和功能

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

CIA (CCG1-interacting factor A)/ASF1, which is the most conserved histone chaperone among the eukaryotes, was genetically identified as a factor for an anti-silencing function (Asf1) by yeast genetic screening. Shortly after that, the CIA-histone-H3-H4 complex was isolated from Drosophila as a histone chaperone CAF-1 stimulator. Human CIA-Ⅰ/Ⅱ (ASF1a/b) was identified as a histone chaperone that interacts with the bromodomain—an acetylated-histone-recognizing domain—of CCG1, in the general transcription initiation factor TFIID. Intensive studies have revealed that CIA/ ASF1 mediates nucleosome assembly by forming a complex with another histone chaperone in human cells and yeast, and is involved in DNA replication, transcription, DNA repair and silencing/anti-silencing in yeast. CIA/ASF1 was shown as a major storage chaperone for soluble histones in proliferating human cells. Despite all these biochemical and biological functional analyses, the structure-function relationship of the nucleosome assembly/disassembly activity of CIA/ASF1 has remained elusive. Here we report the crystal structure, at 2.7 A resolution, of CIA-Ⅰ in complex with histones H3 and H4. The structure shows the histone H3-H4 dimer's mutually exclusive interactions with another histone H3-H4 dimer and CIA-Ⅰ. The carboxy-terminal β-strand of histone H4 changes its partner from the β-strand in histone H2A to that of CIA-Ⅰ through large conformational change. In vitro functional analysis demonstrated that CIA-Ⅰ has a histone H3-H4 tetramer-disruptmg activity. Mutants with weak histone H3-H4 dimer binding activity showed critical functional effects on cellular processes related to transcription. The histone H3-H4 tetramer-disrupting activity of CIA/ASF1 and the crystal structure of the CIA/ASF1-histone-H3-H4 dimer complex should give insights into mechanisms of both nucleosome assembly/disassembly and nucleosome semi-conservative replication.
机译：CIA（CCG1相互作用因子A）/ ASF1是真核生物中最保守的组蛋白伴侣，通过酵母基因筛选已被遗传鉴定为抗沉默功能（Asf1）的因子。此后不久，从果蝇中分离出CIA-组蛋白-H3-H4复合物作为组蛋白伴侣CAF-1刺激物。人类CIA-Ⅰ/Ⅱ（ASF1a / b）被鉴定为组蛋白伴侣，它与一般转录起​​始因子TFIID中CCG1的溴结构域（乙酰化组蛋白识别结构域）相互作用。深入的研究表明，CIA / ASF1通过与人细胞和酵母中的另一种组蛋白伴侣形成复合物来介导核小体装配，并参与酵母中的DNA复制，转录，DNA修复和沉默/抗沉默。 CIA / ASF1被证明是人类细胞增殖中可溶性组蛋白的主要储存伴侣。尽管进行了所有这些生化和生物学功能分析，但CIA / ASF1核小体装配/拆卸活性的结构-功能关系仍然难以捉摸。在这里，我们报道了CIA-Ⅰ与组蛋白H3和H4的复合晶体结构，分辨率为2.7A。该结构显示了组蛋白H3-H4二聚体与另一个组蛋白H3-H4二聚体和CIA-Ⅰ的互斥相互作用。组蛋白H4的羧基末端β链通过大量构象变化将其伴侣从组蛋白H2A的β链变为CIA-Ⅰ。体外功能分析表明，CIA-Ⅰ具有组蛋白H3-H4四聚体破坏活性。组蛋白H3-H4二聚体结合活性弱的突变体对与转录相关的细胞过程显示出关键的功能作用。 CIA / ASF1的组蛋白H3-H4破坏四聚体的活性和CIA / ASF1-histone-H3-H4二聚体复合物的晶体结构应提供有关核小体组装/拆卸和核小体半保守复制机制的见解。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号