Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin
Regional centromeres in the yeast Candida lusitaniae lack pericentromeric heterochromatin
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DOI：
10.1073/pnas.1508749112
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发表时间：
2015-09-29
影响因子：
11.1
通讯作者：
Rusche, Laura N.
中科院分区：
文献类型：
--
作者：
Kapoor, Shivali;Zhu, Lisha;Rusche, Laura N.
点着丝粒是由一个短的共有序列，种子动粒形成，而区域着丝粒缺乏保守序列，而是表观遗传。区域性着丝粒两侧通常是异染色质，以确保高水平的粘着蛋白，并促进忠实的染色体分离。然而，尚不清楚区域着丝粒是否需要着丝粒周围异染色质。在酵母假丝酵母lusitaniae，我们确定了一个独特的类型的区域着丝粒，缺乏着丝粒周围异染色质。着丝粒位置通过两个关键着丝粒蛋白Cse 4和Mif 2的ChIP测序确定，并且与生物信息学预测一致。每个染色体的着丝粒DNA序列是独特的，跨度为4-4.5 kbp，与区域表观遗传学遗传的着丝粒一致。然而，与其他区域性着丝粒不同的是，在C.卢西塔尼亚。特别是，侧翼基因的表达水平与基因组的其余部分相似，插入着丝粒附近的URA 3报告基因不受抑制。此外，着丝粒核心侧翼区域与低乙酰化组蛋白或在其他酵母中产生异染色质的沉默调节蛋白脱乙酰酶无关。有趣的是，着丝粒染色质具有独特的组蛋白修饰模式，富含甲基化的H3 K79和H3 R2，但缺乏在其他区域着丝粒中发现的H3 K4的甲基化。因此，并非所有的区域着丝粒都需要侧翼异染色质。
Point centromeres are specified by a short consensus sequence that seeds kinetochore formation, whereas regional centromeres lack a conserved sequence and instead are epigenetically inherited. Regional centromeres are generally flanked by heterochromatin that ensures high levels of cohesin and promotes faithful chromosome segregation. However, it is not known whether regional centromeres require pericentromeric heterochromatin. In the yeast Candida lusitaniae, we identified a distinct type of regional centromere that lacks pericentromeric heterochromatin. Centromere locations were determined by ChIP-sequencing of two key centromere proteins, Cse4 and Mif2, and are consistent with bioinformatic predictions. The centromeric DNA sequence was unique for each chromosome and spanned 4-4.5 kbp, consistent with regional epigenetically inherited centromeres. However, unlike other regional centromeres, there was no evidence of pericentromeric heterochromatin in C. lusitaniae. In particular, flanking genes were expressed at a similar level to the rest of the genome, and a URA3 reporter inserted adjacent to a centromere was not repressed. In addition, regions flanking the centromeric core were not associated with hypoacetylated histones or a sirtuin deacetylase that generates heterochromatin in other yeast. Interestingly, the centromeric chromatin had a distinct pattern of histone modifications, being enriched for methylated H3K79 and H3R2 but lacking methylation of H3K4, which is found at other regional centromeres. Thus, not all regional centromeres require flanking heterochromatin.