Switching the centromere on and off: epigenetic chromatin alterations provide plasticity in centromere activity stabilizing aberrant dicentric chromosomes
Switching the centromere on and off: epigenetic chromatin alterations provide plasticity in centromere activity stabilizing aberrant dicentric chromosomes
复制标题
打开和关闭着丝粒：表观遗传染色质改变提供了着丝粒活性的可塑性，稳定了异常双着丝粒染色体
DOI：
10.1042/bst20130136
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发表时间：
2013
影响因子：
3.9
通讯作者：
齋藤成昭
中科院分区：
文献类型：
--
作者：
佐藤浩;齋藤成昭
着丝点形成于一个特定的染色体位点，称为着丝粒，在有丝分裂和减数分裂期间调节染色体和纺锤体之间的相互作用。异常的染色体重排和/或新着丝粒的形成可导致单个染色体上存在多个着丝粒，从而导致染色体断裂或细胞周期停滞。对人工双中心染色体的分析表明，着丝粒的活性受表观遗传调控；在一些稳定维持的双中心染色体上，尽管DNA序列保持完整，但其中一个着丝粒不再作为着丝点形成的平台。这种表观遗传着丝粒失活发生在含有“区域着丝粒”的各种真核生物的细胞中，如玉米、裂变酵母和人类的细胞，这表明活性着丝粒的位置是由染色体上的表观遗传标记而不是核苷酸序列决定的。我们最近在分裂酵母中的发现表明，表观遗传着丝粒失活包括两个步骤：着丝粒的解体启动失活，随后的异染色质化阻止失活的着丝粒的复活。在正常衰老的人类细胞中，也观察到着丝粒解体后的异染色质化。因此，表观遗传着丝粒失活不仅可以稳定异常产生的双中心染色体，而且可能是调节细胞增殖的内在机制的一部分。
The kinetochore, which forms on a specific chromosomal locus called the centromere, mediates interactions between the chromosome and the spindle during mitosis and meiosis. Abnormal chromosome rearrangements and/or neocentromere formation can cause the presence of multiple centromeres on a single chromosome, which results in chromosome breakage or cell cycle arrest. Analyses of artificial dicentric chromosomes suggested that the activity of the centromere is regulated epigenetically; on some stably maintained dicentric chromosomes, one of the centromeres no longer functions as a platform for kinetochore formation, although the DNA sequence remains intact. Such epigenetic centromere inactivation occurs in cells of various eukaryotes harbouring ‘regional centromeres’, such as those of maize, fission yeast and humans, suggesting that the position of the active centromere is determined by epigenetic markers on a chromosome rather than the nucleotide sequence. Our recent findings in fission yeast revealed that epigenetic centromere inactivation consists of two steps: disassembly of the kinetochore initiates inactivation and subsequent heterochromatinization prevents revival of the inactivated centromere. Kinetochore disassembly followed by heterochromatinization is also observed in normal senescent human cells. Thus epigenetic centromere inactivation may not only stabilize abnormally generated dicentric chromosomes, but also be part of an intrinsic mechanism regulating cell proliferation.