The unconventional structure of centromeric nucleosomes.

The unconventional structure of centromeric nucleosomes.
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DOI:
10.1007/s00412-012-0372-y
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发表时间:
2012-08
期刊:
影响因子:
1.6
通讯作者:
Furuyama T
Furuyama T
中科院分区:
生物学3区
文献类型:
--
作者:
Henikoff S;Furuyama T

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着丝粒是真核生物染色体的一个重要特征,在有丝分裂和减数分裂中,它是连接纺锤体微管和分离到两极所必需的。着丝粒身份的基本单位是着丝粒特异性核小体,其中着丝粒组蛋白3(cenH 3)变体取代H3。cenH 3核小体的结构一直是争议的主题,因为已经提出了相互排斥的模型,包括常规和非常规的左手八聚体(八体),具有非组蛋白蛋白成分的六聚体和右手异型四聚体(半体)。半体已经从天然的着丝粒染色质中分离出来,但是传统的核小体组装方案通常产生部分未包裹的左手八聚体核小体。在芽殖酵母中,拓扑分析和高分辨率作图揭示了一个单一的右手cenH 3半体占据每条染色体的~80-bp着丝粒DNA元件II(CDEII)。cenH 3的过度生产导致八倍体大小的颗粒在整个酵母基因组中混杂的低水平掺入。我们提出,右手cenH 3半体是着丝粒染色质的通用单位,部分未包裹的左手cenH 3八聚体的固有不稳定性是一种适应,以防止形成染色体臂上的新着丝粒。
The centromere is a defining feature of the eukaryotic chromosome, required for attachment to spindle microtubules and segregation to the poles at both mitosis and meiosis. The fundamental unit of centromere identity is the centromere-specific nucleosome, in which the centromeric histone 3 (cenH3) variant takes the place of H3. The structure of the cenH3 nucleosome has been the subject of controversy, as mutually exclusive models have been proposed, including conventional and unconventional left-handed octamers (octasomes), hexamers with non-histone protein constituents, and right-handed heterotypic tetramers (hemisomes). Hemisomes have been isolated from native centromeric chromatin, but traditional nucleosome assembly protocols have generally yielded partially unwrapped left-handed octameric nucleosomes. In budding yeast, topology analysis and high-resolution mapping has revealed that a single right-handed cenH3 hemisome occupies the ~80-bp Centromere DNA Element II (CDEII) of each chromosome. Overproduction of cenH3 leads to promiscuous low-level incorporation of octasome-sized particles throughout the yeast genome. We propose that the right-handed cenH3 hemisome is the universal unit of centromeric chromatin, and that the inherent instability of partially unwrapped left-handed cenH3 octamers is an adaptation to prevent formation of neocentromeres on chromosome arms.
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