Structure, dynamics, and evolution of centromeric nucleosomes
Structure, dynamics, and evolution of centromeric nucleosomes
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DOI：
10.1073/pnas.0707648104
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发表时间：
2007-10-09
影响因子：
11.1
通讯作者：
Henikoff, Steven
中科院分区：
文献类型：
--
作者：
Dalai, Yamini;Furuyama, Takehito;Henikoff, Steven
着丝粒是真核染色体的标志性特征，为有丝分裂和减数分裂过程中的分离提供附着位点。着丝粒结构的基本单位是着丝粒核小体，它与常规核小体的不同之处在于存在一种着丝粒特异性组蛋白变体（CenH3），取代了标准的H3。我们已经表明，在果蝇间期细胞中发现的CenH3核小体核心是一种异型四聚体，即一个“半核小体”，由CenH3、H4、H2A和H2B各一个分子组成，而不是在大量核小体中发现的标准组蛋白八聚体。在着丝粒处发现半核小体这一惊人发现，要求对长期以来依据更常规核小体进行解释的证据进行重新评估。我们描述了着丝粒核小体的半核小体结构如何解释着丝粒的神秘特性，包括动粒可及性、表观遗传继承、错误掺入的CenH3的快速周转以及着丝粒周围异染色质的转录沉默。由环1介导的结构差异被认为可以解释含有CenH3的稳定四聚体而非含有H3的稳定八聚体的形成。不对称的CenH3半核小体可能会中断八聚体H3阵列的整体浓缩，并为动粒形成提供一个不对称的表面。我们认为，这种区分着丝粒核小体和包装核小体的简单机制是在真核生物进化初期从类似古菌的祖先演化而来的。
Centromeres are defining features of eukaryotic chromosomes, providing sites of attachment for segregation during mitosis and meiosis. The fundamental unit of centromere structure is the centromeric nucleosome, which differs from the conventional nucleosome by the presence of a centromere-specific histone variant (CenH3) in place of canonical H3. We have shown that the CenH3 nucleosome core found in interphase Drosophila cells is a heterotypic tetramer, a "hemisome" consisting of one molecule each of CenH3 H4, H2A, and H2B, rather than the octamer of canonical histones that is found in bulk nucleosomes. The surprising discovery of hemisomes at centromeres calls for a reevaluation of evidence that has long been interpreted in terms of a more conventional nucleosome. We describe how the hemisome structure of centromeric nucleosomes can account for enigmatic properties of centromeres, including kinetochore accessibility, epigenetic inheritance, rapid turnover of misincorporated CenH3, and transcriptional quiescence of pericentric heterochromatin. Structural differences mediated by loop 1 are proposed to account for the formation of stable tetramers containing CenH3 rather than stable octamers containing H3. Asymmetric CenH3 hemisomes might interrupt the global condensation of octameric H3 arrays and present an asymmetric surface for kinetochore formation. We suggest that this simple mechanism for differentiation between centromeric and packaging nucleosomes evolved from an archaea like ancestor at the dawn of eukaryotic evolution.