Ccp1同二聚体通过拮抗CENP-A加载来介导染色质完整性。
Ccp1 Homodimer Mediates Chromatin Integrity by Antagonizing CENP-A Loading.
作者信息
Dong Qianhua, Yin Feng-Xiang, Gao Feng, Shen Yuan, Zhang Faben, Li Yang, He Haijin, Gonzalez Marlyn, Yang Jinpu, Zhang Shu, Su Min, Chen Yu-Hang, Li Fei
机构信息
Department of Biology, New York University, New York, NY 10003, USA.
University of Chinese Academy of Sciences, Beijing 100101, China.
出版信息
Mol Cell. 2016 Oct 6;64(1):79-91. doi: 10.1016/j.molcel.2016.08.022. Epub 2016 Sep 22.
CENP-A is a centromere-specific histone 3 variant essential for centromere specification. CENP-A partially replaces canonical histone H3 at the centromeres. How the particular CENP-A/H3 ratio at centromeres is precisely maintained is unknown. It also remains unclear how CENP-A is excluded from non-centromeric chromatin. Here, we identify Ccp1, an uncharacterized NAP family protein in fission yeast that antagonizes CENP-A loading at both centromeric and non-centromeric regions. Like the CENP-A loading factor HJURP, Ccp1 interacts with CENP-A and is recruited to centromeres at the end of mitosis in a Mis16-dependent manner. These data indicate that factors with opposing CENP-A loading activities are recruited to centromeres. Furthermore, Ccp1 also cooperates with H2A.Z to evict CENP-A assembled in euchromatin. Structural analyses indicate that Ccp1 forms a homodimer that is required for its anti-CENP-A loading activity. Our study establishes mechanisms for maintenance of CENP-A homeostasis at centromeres and the prevention of ectopic assembly of centromeres.
着丝粒蛋白A（CENP-A）是一种着丝粒特异性组蛋白H3变体，对于着丝粒的指定至关重要。CENP-A在着丝粒处部分取代了经典组蛋白H3。目前尚不清楚着丝粒处特定的CENP-A/H3比例是如何精确维持的。CENP-A如何被排除在非着丝粒染色质之外也仍不清楚。在此，我们鉴定出裂殖酵母中一种未被表征的NAP家族蛋白Ccp1，它在着丝粒和非着丝粒区域均拮抗CENP-A的装载。与CENP-A装载因子HJURP一样，Ccp1与CENP-A相互作用，并在有丝分裂末期以依赖Mis16的方式被招募到着丝粒。这些数据表明，具有相反CENP-A装载活性的因子被招募到着丝粒。此外，Ccp1还与H2A.Z协同作用，以驱逐在常染色质中组装的CENP-A。结构分析表明，Ccp1形成同源二聚体，这是其抗CENP-A装载活性所必需的。我们的研究建立了着丝粒处CENP-A稳态维持以及防止着丝粒异位组装的机制。
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