The Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3.

The Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3.
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DOI:
10.1038/s41467-017-00704-3
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发表时间:
2017-09-13
影响因子:
16.6
通讯作者:
Lee D
Lee D
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Choi ES;Cheon Y;Kang K;Lee D

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着丝粒是染色体上的一个位点,在此位点上,动粒被组装以指导染色体分离。已知组蛋白H3变体,着丝粒蛋白A(CENP-A),在表观遗传学上标记活性着丝粒,但是CENP-A在着丝粒处繁殖,取代组蛋白H3的机制仍然知之甚少。使用裂殖酵母,在这里,我们表明,Ino 80腺苷三磷酸(ATP)依赖的染色质重塑复合物,去除组蛋白H3含有核小体相关的染色质,促进CENP-ACnp 1染色质组装在着丝粒在一个冗余的方式与另一个染色质重塑因子Chd 1Hrp 1。CENP-ACnp 1染色质主动募集Ino 80复合物至着丝粒,以引起含组蛋白H3的核小体的驱逐。将Ino 80亚基人工靶向至置于天然着丝粒中的非着丝粒DNA序列增强了CENP-ACnp 1染色质向非着丝粒DNA中的扩散。基于这些结果,我们提出CENP-ACnp 1染色质采用Ino 80复合物介导CENP-ACnp 1替换组蛋白H3,从而增强自身。组蛋白变体CENP-A标记活跃的着丝粒,并通过一种知之甚少的机制在着丝粒处取代H3。在这里,作者提供的证据表明,染色质重塑Ino 80促进CENP-A染色质组装在着丝粒分裂酵母。
The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-ACnp1 chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1Hrp1. CENP-ACnp1 chromatin actively recruits the Ino80 complex to centromeres to elicit eviction of histone H3-containing nucleosomes. Artificial targeting of Ino80 subunits to a non-centromeric DNA sequence placed in a native centromere enhances the spreading of CENP-ACnp1 chromatin into the non-centromeric DNA. Based on these results, we propose that CENP-ACnp1 chromatin employs the Ino80 complex to mediate the replacement of histone H3 with CENP-ACnp1, and thereby reinforces itself. The histone variant CENP-A marks active centromeres and replaces H3 at centromeres through a poorly understood mechanism. Here, the authors provide evidence that the chromatin remodeller Ino80 promotes CENP-A chromatin assembly at the centromere in fission yeast.
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