HJURP is involved in the expansion of centromeric chromatin.
HJURP is involved in the expansion of centromeric chromatin.
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DOI：
10.1091/mbc.e15-02-0094
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发表时间：
2015-08-01
影响因子：
3.3
通讯作者：
Fukagawa T
中科院分区：
文献类型：
--
作者：
Perpelescu M;Hori T;Toyoda A;Misu S;Monma N;Ikeo K;Obuse C;Fujiyama A;Fukagawa T
HJURP表现出可与其CENP-A结合活性分离的着丝粒扩增活性。有人建议，这种着丝粒扩展活动反映了HJURP，它使用这种活动，以促进塑料的着丝粒染色质结构的建立的功能特性。CENP-A特异性伴侣HJURP介导CENP-A在着丝粒处的沉积。HJURP的N-末端区域负责与可溶性CENP-A结合。然而，目前还不清楚是否HJURP的其他区域有额外的功能，为着丝粒的形成和维护。在这项研究中，我们建立了鸡DT 40基因敲除细胞系和HJURP的基因置换构建体，以评估HJURP在体内的其他功能。我们的分析表明，HJURP的中间区域与Mis 18复合蛋白M18 BP 1/KNL 2相关，并且HJURP-M18 BP 1的相关性是HJURP功能所必需的。此外，在异位HJURP定位诱导的人工着丝粒分析的基础上，我们证明了HJURP表现出着丝粒扩展活性，这是从其CENP-A结合活性分离。我们还观察到HJURP过表达后，自然着丝粒周围的着丝粒扩张。我们建议，这种着丝粒扩展活动反映了HJURP的功能特性，它使用这种活动，以促进塑料的着丝粒染色质结构的建立。
HJURP exhibits a centromere expansion activity that is separable from its CENP-A–binding activity. It is proposed that this centromere expansion activity reflects the functional properties of HJURP, which uses this activity to contribute to the plastic establishment of a centromeric chromatin structure. The CENP-A–specific chaperone HJURP mediates CENP-A deposition at centromeres. The N-terminal region of HJURP is responsible for binding to soluble CENP-A. However, it is unclear whether other regions of HJURP have additional functions for centromere formation and maintenance. In this study, we generated chicken DT40 knockout cell lines and gene replacement constructs for HJURP to assess the additional functions of HJURP in vivo. Our analysis revealed that the middle region of HJURP associates with the Mis18 complex protein M18BP1/KNL2 and that the HJURP-M18BP1 association is required for HJURP function. In addition, on the basis of the analysis of artificial centromeres induced by ectopic HJURP localization, we demonstrate that HJURP exhibits a centromere expansion activity that is separable from its CENP-A–binding activity. We also observed centromere expansion surrounding natural centromeres after HJURP overexpression. We propose that this centromere expansion activity reflects the functional properties of HJURP, which uses this activity to contribute to the plastic establishment of a centromeric chromatin structure.