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首页> 外文期刊>Nucleus >CENP-C facilitates the recruitment of M18BP1 to centromeric chromatin
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CENP-C facilitates the recruitment of M18BP1 to centromeric chromatin

机译：CENP-C促进M18BP1募集到着丝粒染色质

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摘要

Centromeres are important structural constituents of chromosomes that ensure proper chromosome segregation during mitosis by providing defined sites for kinetochore attachment. In higher eukaryotes, centromeres have no specific DNA sequence and thus, they are rather determined through epigenetic mechanisms. A fundamental process in centromere establishment is the incorporation of the histone variant CENP-A into centromeric chromatin, which provides a binding platform for the other centromeric proteins. The Mis18 complex, and, in particular, its member M18BP1 was shown to be essential for both incorporation and maintenance of CENP-A.Here we show that M18BP1 displays a cell cycle-regulated association with centromeric chromatin in mouse embryonic stem cells. M18BP1 is highly enriched at centromeric regions from late anaphase through to G1 phase. An interaction screen against 16 core centromeric proteins revealed a novel interaction of M18BP1 with CENP-C. We mapped the interaction domain in M18BP1 to a central region containing a conserved SANT domain and in CENP-C to the C-terminus. Knock-down of CENP-C leads to reduced M18BP1 association and lower CENP-A levels at centromeres, suggesting that CENP-C works as an important factor for centromeric M18BP1 recruitment and thus for maintaining centromeric CENP-A.
机译：着丝粒是染色体的重要结构组成部分，通过提供确定的线粒体附着位点，可确保有丝分裂期间染色体的正确隔离。在高级真核生物中，着丝粒没有特定的DNA序列，因此，它们是通过表观遗传机制确定的。着丝粒建立的基本过程是将组蛋白变异体CENP-A掺入着丝粒染色质中，该染色质为其他着丝粒蛋白提供了结合平台。已证明Mis18复合物，尤其是其成员M18BP1对于CENP-A的掺入和维持都是必不可少的。在这里，我们显示M18BP1在小鼠胚胎干细胞中显示出与着丝粒染色质的细胞周期调控的缔合。从后期后期到G1期，M18BP1在着丝粒区域高度富集。针对16种核心着丝粒蛋白的相互作用筛选揭示了M18BP1与CENP-C的新型相互作用。我们将M18BP1中的相互作用域映射到包含保守SANT域的中央区域，并将CENP-C映射到C末端。敲低CENP-C会导致着丝粒处M18BP1缔合减少并降低CENP-A水平，这表明CENP-C作为着丝粒M18BP1募集并因此维持着丝粒CENP-A的重要因素。

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