ACF catalyses chromatosome movements in chromatin fibres

ACF catalyses chromatosome movements in chromatin fibres
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DOI:
10.1038/sj.emboj.7601902
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发表时间:
2008-03-19
期刊:
影响因子:
11.4
通讯作者:
Becker, Peter B.
Becker, Peter B.
中科院分区:
生物学1区
文献类型:
--
作者:
Maier, Verena K.;Chioda, Mariacristina;Becker, Peter B.

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含有 ATP 酶 ISWI 的核小体重塑因子(例如 ACF)通过促进组蛋白八聚体的滑动,使染色质中的 DNA 变得可接近。尽管单核小体的 ATP 依赖性重新定位在体外很容易观察到,但尚不清楚核小体在生理染色质中的移动程度,其中邻近的核小体、连接组蛋白和核小体阵列的折叠限制了移动性。我们从定义的组件中组装了由 12 个核小体或 12 个染色体(核小体加连接组蛋白)组成的阵列,并通过 ACF 或 ATPase CHD1 对它们进行重构。这两个因素都增加了核小体阵列中 DNA 的获取。 ACF(而非 CHD1)催化了整个阵列中核小体的深刻运动,表明了不同的重塑机制。连接组蛋白抑制 CHD1 的重塑。令人惊讶的是,ACF 催化了含有饱和水平连接组蛋白 H1 的染色质中整个染色体的显着重新定位。 H1 仅抑制 ATP 依赖性 DNA 可及性生成约 50%。催化染色体运动的首次证明表明,大量的间期常染色质可能通过专门的核小体重塑因子而呈现动态。
Nucleosome-remodelling factors containing the ATPase ISWI, such as ACF, render DNA in chromatin accessible by promoting the sliding of histone octamers. Although the ATP-dependent repositioning of mononucleosomes is readily observable in vitro, it is unclear to which extent nucleosomes can be moved in physiological chromatin, where neighbouring nucleosomes, linker histones and the folding of the nucleosomal array restrict mobility. We assembled arrays consisting of 12 nucleosomes or 12 chromatosomes ( nucleosomes plus linker histone) from defined components and subjected them to remodelling by ACF or the ATPase CHD1. Both factors increased the access to DNA in nucleosome arrays. ACF, but not CHD1, catalysed profound movements of nucleosomes throughout the array, suggesting different remodelling mechanisms. Linker histones inhibited remodelling by CHD1. Surprisingly, ACF catalysed significant repositioning of entire chromatosomes in chromatin containing saturating levels of linker histone H1. H1 inhibited the ATP-dependent generation of DNA accessibility by only about 50%. This first demonstration of catalysed chromatosome movements suggests that the bulk of interphase euchromatin may be rendered dynamic by dedicated nucleosome-remodelling factors.