Fujita Yohta, Hayashi Takeshi, Kiyomitsu Tomomi, Toyoda Yusuke, Kokubu Aya, Obuse Chikashi, Yanagida Mitsuhiro
CREST Research Project of Japan Science and Technology Corporation (JST), Graduate School of Biostudies, Kyoto University, Yoshida-Honmachi, Kyoto 606-8501, Japan.
Dev Cell. 2007 Jan;12(1):17-30. doi: 10.1016/j.devcel.2006.11.002.
The centromere is the chromosomal site that joins to microtubules during mitosis for proper segregation. Determining the location of a centromere-specific histone H3 called CENP-A at the centromere is vital for understanding centromere structure and function. Here, we report the identification of three human proteins essential for centromere/kinetochore structure and function, hMis18alpha, hMis18beta, and M18BP1, the complex of which is accumulated specifically at the telophase-G1 centromere. We provide evidence that such centromeric localization of hMis18 is essential for the subsequent recruitment of de novo-synthesized CENP-A. If any of the three is knocked down by RNAi, centromere recruitment of newly synthesized CENP-A is rapidly abolished, followed by defects such as misaligned chromosomes, anaphase missegregation, and interphase micronuclei. Tricostatin A, an inhibitor to histone deacetylase, suppresses the loss of CENP-A recruitment to centromeres in hMis18alpha RNAi cells. Telophase centromere chromatin may be primed or licensed by the hMis18 complex and RbAp46/48 to recruit CENP-A through regulating the acetylation status in the centromere.
着丝粒是在有丝分裂期间与微管相连以实现正确分离的染色体位点。确定一种名为CENP - A的着丝粒特异性组蛋白H3在着丝粒上的位置对于理解着丝粒的结构和功能至关重要。在此，我们报告鉴定出三种对着丝粒/动粒结构和功能至关重要的人类蛋白质，即hMis18α、hMis18β和M18BP1，它们的复合物特异性地聚集在末期 - G1期着丝粒处。我们提供的证据表明，hMis18的这种着丝粒定位对于随后从头合成的CENP - A的募集至关重要。如果通过RNA干扰敲低这三种蛋白质中的任何一种，新合成的CENP - A对着丝粒的募集会迅速被消除，随后会出现诸如染色体排列不齐、后期错误分离和间期微核等缺陷。曲古抑菌素A，一种组蛋白脱乙酰酶抑制剂，可抑制hMis18α RNA干扰细胞中CENP - A对着丝粒募集的丧失。末期着丝粒染色质可能由hMis18复合物和RbAp46/48启动或许可，以通过调节着丝粒中的乙酰化状态来募集CENP - A。
