Plasticity and Epigenetic Inheritance of Centromere-specific Histone H3 (CENP-A)-containing Nucleosome Positioning in the Fission Yeast*
Plasticity and Epigenetic Inheritance of Centromere-specific Histone H3 (CENP-A)-containing Nucleosome Positioning in the Fission Yeast*
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DOI：
10.1074/jbc.m113.471276
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发表时间：
2013-05
期刊：
影响因子：
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通讯作者：
Jianhui Yao;Xingkun Liu;T. Sakuno;Wenzhu Li;Y. Xi;Pavithra Aravamudhan;Ajit P. Joglekar;Wei Li;Yoshinori Watanabe;Xiangwei He
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文献类型：
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作者：
Jianhui Yao;Xingkun Liu;T. Sakuno;Wenzhu Li;Y. Xi;Pavithra Aravamudhan;Ajit P. Joglekar;Wei Li;Yoshinori Watanabe;Xiangwei He
背景：CENP-A核小体支持动粒组装。结果：Cnp 1/CENP-A占用，表示沉默的报告基因，基因同源细胞之间的变化。结论：着丝粒染色质结构是灵活的，可表观遗传。重要性：CENP-A核小体如何遗传对于每个染色体组装一个功能性着丝粒具有潜在的重要性，并且可以作为阐明表观遗传遗传的一般机制的实验系统。含有特异性组蛋白H3变体CENP-A的核小体标记每个染色质上的着丝粒位点并启动动粒组装。对于常见类型的区域着丝粒，知之甚少的分子细节的着丝粒染色质组织，其传播通过细胞分裂，以及不同的组织模式可能促进动粒组装。在这里，我们表明，在裂变酵母S。在粟酒裂殖酵母中，在着丝粒核心内发现相对少量的CENP-A/Cnp 1核小体，并且它们相对于基础DNA的定位在遗传同质的细胞中变化。与Cnp 1核小体的灵活定位一致，大部分内源性着丝粒因其介导染色体分离的基本活性而被破坏。我们提出的生化证据表明Cnp 1的占据与潜在报告基因的沉默直接相关。此外，使用新开发的谱系分析测定，我们证明了Cnp 1定位的表观遗传，并量化了整个细胞世代中Cnp 1核小体偶尔重新定位的速率。总之，我们的研究结果揭示了可塑性和表观遗传遗传的性质，着丝粒染色质组织。
Background: CENP-A nucleosomes support kinetochore assembly. Results: Cnp1/CENP-A occupancy, indicated by silencing of the reporter gene, varies among genetically homogenous cells. Conclusion: Centromeric chromatin organization is flexible and inherited epigenetically. Significance: How CENP-A nucleosomes are inherited is potentially important for assembling one functional centromere per chromosome and may serve as an experimental system to elucidate the general mechanisms for epigenetic inheritance. Nucleosomes containing the specific histone H3 variant CENP-A mark the centromere locus on each chromatin and initiate kinetochore assembly. For the common type of regional centromeres, little is known in molecular detail of centromeric chromatin organization, its propagation through cell division, and how distinct organization patterns may facilitate kinetochore assembly. Here, we show that in the fission yeast S. pombe, a relatively small number of CENP-A/Cnp1 nucleosomes are found within the centromeric core and that their positioning relative to underlying DNA varies among genetically homogenous cells. Consistent with the flexible positioning of Cnp1 nucleosomes, a large portion of the endogenous centromere is dispensable for its essential activity in mediating chromosome segregation. We present biochemical evidence that Cnp1 occupancy directly correlates with silencing of the underlying reporter genes. Furthermore, using a newly developed pedigree analysis assay, we demonstrated the epigenetic inheritance of Cnp1 positioning and quantified the rate of occasional repositioning of Cnp1 nucleosomes throughout cell generations. Together, our results reveal the plasticity and the epigenetically inheritable nature of centromeric chromatin organization.