Cryo-electron microscopy structure of the H3-H4 octasome: A nucleosome-like particle without histones H2A and H2B.
Cryo-electron microscopy structure of the H3-H4 octasome: A nucleosome-like particle without histones H2A and H2B.
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DOI：
10.1073/pnas.2206542119
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发表时间：
2022-11-08
影响因子：
11.1
通讯作者：
Kurumizaka, Hitoshi
中科院分区：
文献类型：
--
作者：
Nozawa, Kayo;Takizawa, Yoshimasa;Pierrakeas, Leonidas;Sogawa-Fujiwara, Chizuru;Saikusa, Kazumi;Akashi, Satoko;Luk, Ed;Kurumizaka, Hitoshi
遗传信息储存在染色质中，以核小体为基本单位。一个典型的核小体由一个八聚体核心组成，由两个拷贝的组蛋白H_2A-H_2B二聚体和H_3-H_4二聚体组成，由一圈半的DNA包裹。在本研究中，我们确定了一种名为H3-H4八聚体的非传统核蛋白颗粒的结构，它的核心由四个不含H_2A-H_2B的人H_3-H_4二聚体组成，DNA以核小体的形式包裹在这个核心上。在酵母中发现了在人类H3-H4八体结构中观察到的组蛋白-组蛋白相互作用。将H3-H4八体整合到真核基因组中可能会改变染色质的结构和动力学，代表着我们对表观基因组调控的理解的范式转变。核小体是真核生物染色质的主要包装单位，核小体的八聚体核心由两个组蛋白H_2A-H_2B和H_3-H_4二聚体组成，其周围包裹着∼的147bpDNA。具有替代组蛋白化学计量和DNA包裹构型的非核小体颗粒已经被发现，它们可以深刻地影响基因组的结构和功能。利用冷冻电子显微镜，我们解决了H3-H4八聚体的结构，这是一种核小体样粒子，其核心是两个四聚体，仅由H3和H4组蛋白组成。核心被∼120bp的DNA以1.5个负超螺旋转数包裹，形成两个堆叠的圆盘，由H4-H4‘四螺旋束连接。观察到与不同的盘间夹角对应的三种构象，表明H3-H4八体结构的柔性。体内交联实验检测到组蛋白-组蛋白相互作用符合H3-H4八酶体模型，提示细胞中存在H3-H4八酶体或相关结构特征。
Genetic information is stored in chromatin, with nucleosomes as the basic unit. A typical nucleosome comprises an octameric core, consisting of two copies of the histone H2A-H2B dimers and H3-H4 dimers, wrapped by one and a half turns of DNA. In the present study, we determined the structure of an unconventional nucleoprotein particle called the H3-H4 octasome, which has a core composed of four dimers of human H3-H4 without H2A-H2B, with DNA wrapped around this core in a nucleosome-like configuration. Histone–histone interactions observed in the human H3-H4 octasome structure were found in yeast. The incorporation of H3-H4 octasomes into the eukaryotic genome will likely alter chromatin structure and dynamics, representing a paradigm shift in our understanding of epigenome regulation. The canonical nucleosome, which represents the major packaging unit of eukaryotic chromatin, has an octameric core composed of two histone H2A-H2B and H3-H4 dimers with ∼147 base pairs (bp) of DNA wrapped around it. Non-nucleosomal particles with alternative histone stoichiometries and DNA wrapping configurations have been found, and they could profoundly influence genome architecture and function. Using cryo–electron microscopy, we solved the structure of the H3-H4 octasome, a nucleosome-like particle with a di-tetrameric core consisting exclusively of the H3 and H4 histones. The core is wrapped by ∼120 bp of DNA in 1.5 negative superhelical turns, forming two stacked disks that are connected by a H4-H4’ four-helix bundle. Three conformations corresponding to alternative interdisk angles were observed, indicating the flexibility of the H3-H4 octasome structure. In vivo crosslinking experiments detected histone–histone interactions consistent with the H3-H4 octasome model, suggesting that H3-H4 octasomes or related structural features exist in cells.
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影响因子：
48
作者：
Kastner, Berthold;Fischer, Niels;Stark, Holger
通讯作者：
Stark, Holger
影响因子：
2
作者：
Giles, Kevin;Williams, Jonathan P.;Campuzano, Iain
通讯作者：
Campuzano, Iain
影响因子：
2.9
作者：
Arimura, Yasuhiro;Tachiwana, Hiroaki;Kurumizaka, Hitoshi
通讯作者：
Kurumizaka, Hitoshi
影响因子：
7.7
作者：
Bowerman S;Wereszczynski J;Luger K
通讯作者：
Luger K
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH