Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere.
Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere.
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DOI：
10.1126/science.1259308
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发表时间：
2015-05-08
期刊：
影响因子：
--
通讯作者：
Black BE
中科院分区：
文献类型：
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作者：
Falk SJ;Guo LY;Sekulic N;Smoak EM;Mani T;Logsdon GA;Gupta K;Jansen LE;Van Duyne GD;Vinogradov SA;Lampson MA;Black BE
每个染色体的遗传依赖于它的着丝粒。组蛋白H3变体CENP-A对于表观遗传学标记着丝粒位置至关重要。我们发现，CENP-A是定量保留在着丝粒上，它最初组装。CENP-C与CENP-A核小体结合，是稳定着丝粒染色质的主要候选者。使用纯化的组分，我们发现CENP-C重塑CENP-A核小体的八聚体组蛋白核心，硬化表面和内部核小体结构，并调节末端DNA以匹配在功能性人类着丝粒处的天然CENP-A核小体上发现的松散包裹。因此，CENP-C以类似于酶的变构调节的方式影响核小体形状和动力学。CENP-C缺失导致CENP-A从着丝粒快速去除，表明它们在维持着丝粒身份方面的协作。
Inheritance of each chromosome depends upon its centromere. A histone H3 variant, CENP-A, is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity.