Cell-cycle-dependent structural transitions in the human CENP-A nucleosome in vivo.

Cell-cycle-dependent structural transitions in the human CENP-A nucleosome in vivo.
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DOI:
10.1016/j.cell.2012.05.035
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发表时间:
2012-07-20
期刊:
影响因子:
64.5
通讯作者:
Dalal Y
Dalal Y
中科院分区:
生物学1区
文献类型:
--
作者:
Bui M;Dimitriadis EK;Hoischen C;An E;Quénet D;Giebe S;Nita-Lazar A;Diekmann S;Dalal Y

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在真核生物中,DNA被典型的组蛋白包装成染色质。专门的组蛋白H3变体CENP-A通过在着丝粒处替换H3为染色体分离提供了表观遗传和结构基础。与唯一的八聚体规范H3核小体不同,CENP-A核小体已被证明以八聚体、六聚体和四聚体存在。一个有趣的可能性调和这些观察是CENP-A核小体循环之间的八聚体和四聚体在体内。我们通过跟踪CENP-A核小体组分、结构、染色质折叠和整个人类细胞周期的共价修饰来验证这一假设。我们报告说,CENP-A核小体改变从四聚体八聚体复制前和复制后恢复到四聚体。这些结构转变伴随着可逆的伴侣蛋白结合,染色质纤维折叠变化,以及CENP-A和H4的组蛋白折叠结构域中先前未描述的修饰。我们的研究结果揭示了CENP-A核小体结构的周期性,并对着丝粒复制后表观遗传记忆的维持产生了影响。
In eukaryotes, DNA is packaged into chromatin by canonical histone proteins. The specialized histone H3 variant CENP-A provides an epigenetic and structural basis for chromosome segregation by replacing H3 at centromeres. Unlike exclusively octameric canonical H3 nucleosomes, CENP-A nucleosomes have been shown to exist as octamers, hexamers, and tetramers. An intriguing possibility reconciling these observations is that CENP-A nucleosomes cycle between octamers and tetramers in vivo. We tested this hypothesis by tracking CENP-A nucleosomal components, structure, chromatin folding, and covalent modifications across the human cell cycle. We report that CENP-A nucleosomes alter from tetramers to octamers before replication and revert to tetramers after replication. These structural transitions are accompanied by reversible chaperone binding, chromatin fiber folding changes, and previously undescribed modifications within the histone fold domains of CENP-A and H4. Our results reveal a cyclical nature to CENP-A nucleosome structure and have implications for the maintenance of epigenetic memory after centromere replication.
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