Association of M18BP1/KNL2 with CENP-A Nucleosome Is Essential for Centromere Formation in Non-mammalian Vertebrates
Association of M18BP1/KNL2 with CENP-A Nucleosome Is Essential for Centromere Formation in Non-mammalian Vertebrates
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DOI：
10.1016/j.devcel.2017.06.019
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发表时间：
2017-07-24
影响因子：
11.8
通讯作者：
Fukagawa, Tatsuo
中科院分区：
文献类型：
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作者：
Hori, Tetsuya;Shang, Wei-Hao;Fukagawa, Tatsuo
着丝粒是由序列无关的表观遗传机制通过将CENP-A整合到着丝粒中来指定和维持的。鉴于CENP-A的掺入需要Mis18复合体位于着丝粒区域，因此有必要精确了解Mis18复合体如何定位于着丝粒区域。在这里，我们发现在鸡DT40细胞中，Mis18复合物的着丝粒定位取决于CENP-A，而不是CENP-C或CENP-T。此外，我们证明了Mis18复合体的成员M18BP1/KNL2在鸡和其他脊椎动物中含有cenp - c样基元，这对于DT40细胞中的着丝粒定位和M18BP1/KNL2功能至关重要。我们还发现体外重建的CENP-A核小体，而不是H3核小体，结合到含有M18BP1/KNL2的cenp - c样基序上。基于这些结果，我们得出结论，m18bp1 /KNL2在非哺乳动物脊椎动物中通过直接结合CENP-A核小体形成着丝粒是必不可少的。这解释了新的CENP-A如何识别着丝粒位置。
Centromeres are specified and maintained by sequence-independent epigenetic mechanisms through the incorporation of CENP-A into centromeres. Given that CENP-A incorporation requires the Mis18 complex to be in the centromere region, it is necessary to precisely understand how the Mis18 complex localizes to the centromere region. Here, we showed that centromere localization of the Mis18 complex depends on CENP-A, but not CENP-C or CENP-T, in chicken DT40 cells. Furthermore, we demonstrated that M18BP1/KNL2, a member of the Mis18 complex, contained the CENP-C-like motif in chicken and other vertebrates, which is essential for centromere localization and M18BP1/KNL2 function in DT40 cells. We also showed that in vitro reconstituted CENP-A nucleosome, but not H3 nucleosome, bound to the CENP-C-like motif containing M18BP1/KNL2. Based on these results, we conclude thatM18BP1/KNL2 is essential for centromere formation through direct binding to CENP-A nucleosome in non-mammalian vertebrates. This explains how new CENP-A recognizes the centromere position.