The histone variant macro-H2A preferentially forms "hybrid nucleosomes"
The histone variant macro-H2A preferentially forms "hybrid nucleosomes"
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DOI：
10.1074/jbc.m602258200
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发表时间：
2006-09-01
影响因子：
4.8
通讯作者：
Luger, Karolin
中科院分区：
文献类型：
--
作者：
Chakravarthy, Srinivas;Luger, Karolin
宏-H2 A的组蛋白结构域，其构成该组蛋白变体的N-末端三分之一，与主要H2 A仅64%相同。我们以前已经表明，在核小体中，两个H2 A部分都被大分子H2 A取代的主要结构差异在于两个组蛋白二聚体之间的唯一接触点，即大分子H2 A的L1-L1界面。在这里，我们表明，宏H2 A的L1环是负责增加盐依赖性的稳定性的组蛋白八聚体，与核小体组装途径的影响。目前还不清楚核小体中是否只有一个或两个H2 A-H2 B二聚体在体内被含有核小体的H2 A变体取代。我们证明，macroH 2A优先形成杂交核小体含有一个链的主要H2 A和macro-HA在体外。这种混合核小体的2.9埃晶体结构与同型的主要含H2 A和大含H2 A的核小体相比，在L1-L1界面显示出显著的结构差异。同型和杂合大核小体核心颗粒（NCP）均对分子伴侣辅助的H2 A-H2 B二聚体交换具有抗性。总之，我们的研究结果表明，宏H2 A的组蛋白结构域修改核小体的动态特性。我们提出，形成混合宏NCP的可能性增加了另一个层次的复杂性变异核小体的结构和功能。
The histone domain of macro-H2A, which constitutes the N-terminal one third of this histone variant, is only 64% identical to major H2A. We have shown previously that the main structural differences in a nucleosome in which both H2A moieties have been replaced by macro-H2A reside in the only point of contact between the two histone dimers, the L1-L1 interface of macro-H2A. Here we show that the L1 loop of macro-H2A is responsible for the increased salt-dependent stability of the histone octamer, with implications for the nucleosome assembly pathway. It is unknown whether only one or both of the H2A-H2B dimers within a nucleosome are replaced with H2A variant containing nucleosomes in vivo. We demonstrate that macroH2A preferentially forms hybrid nucleosomes containing one chain each of major H2A and macro-HA in vitro. The 2.9-angstrom crystal structure of such a hybrid nucleosome shows significant structural differences in the L1-L1 interface when comparing with homotypic major H2A-and macro-H2A-containing nucleosomes. Both homotypic and hybrid macro-nucleosome core particles ( NCPs) are resistant to chaperone-assisted H2A-H2B dimer exchange. Together, our findings suggest that the histone domain of macro-H2A modifies the dynamic properties of the nucleosome. We propose that the possibility of forming hybrid macro-NCP adds yet another level of complexity to variant nucleosome structure and function.