CENP-B controls centromere formation depending on the chromatin context
CENP-B controls centromere formation depending on the chromatin context
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DOI：
10.1016/j.cell.2007.10.045
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发表时间：
2007-12-28
期刊：
影响因子：
64.5
通讯作者：
Masumoto, Hiroshi
中科院分区：
文献类型：
--
作者：
Okada, Teruaki;Ohzeki, Jun-Ichirou;Masumoto, Hiroshi
着丝粒是一个染色质区域，作为纺锤体附着点，在细胞分裂过程中指导真核染色体的准确遗传。然而，着丝粒在特定基因组区域组装和稳定的机制尚不清楚。人类/哺乳动物人工染色体（HAC/MAC）的重新形成需要含有着丝粒CENP-B蛋白结合基序的α -卫星DNA的存在。我们在这里证明了HAC/MAC上的着丝粒从头组装依赖于CENP-B。相反，当α -卫星DNA整合到染色体位点时，在表达CENP-B的细胞中，着丝粒的形成受到抑制。值得注意的是，在这些整合位点上，CENP-B增强组蛋白H3-K9三甲基化和DNA甲基化，从而刺激异染色质的形成。因此，我们提出CENP-B在着丝粒形成中起双重作用，确保在缺乏功能着丝粒的DNA上重新形成，但防止在染色体上形成多余的着丝粒。
The centromere is a chromatin region that serves as the spindle attachment point and directs accurate inheritance of eukaryotic chromosomes during cell divisions. However, the mechanism by which the centromere assembles and stabilizes at a specific genomic region is not clear. The de novo formation of a human/mammalian artificial chromosome (HAC/MAC) with a functional centromere assembly requires the presence of alpha-satellite DNA containing binding motifs for the centromeric CENP-B protein. We demonstrate here that de novo centromere assembly on HAC/MAC is dependent on CENP-B. In contrast, centromere formation is suppressed in cells expressing CENP-B when alpha-satellite DNA was integrated into a chromosomal site. Remarkably, on those integration sites CENP-B enhances histone H3-K9 trimethylation and DNA methylation, thereby stimulating heterochromatin formation. Thus, we propose that CENP-B plays a dual role in centromere formation, ensuring de novo formation on DNA lacking a functional centromere but preventing the formation of excess centromeres on chromosomes.