Structural determinants for generating centromeric chromatin
Structural determinants for generating centromeric chromatin
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DOI：
10.1038/nature02766
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发表时间：
2004-07-29
期刊：
影响因子：
64.8
通讯作者：
Cleveland, DW
中科院分区：
文献类型：
--
作者：
Black, BE;Foltz, DR;Cleveland, DW
哺乳动物的着丝粒不是由共有DNA序列定义的。在所有真核生物中，功能性着丝粒的一个标志-正常着丝粒和在非典型位点异常形成的着丝粒-是着丝粒蛋白A（CENP-A）的积累，CENP-A是一种组蛋白变体，在着丝粒核小体中取代H3（1-7）。在这里，我们使用氘交换/质谱结合流体动力学措施，CENP-A和组蛋白H4形成亚核小体四聚体，比相应的组蛋白H3和H4四聚体更紧凑，构象更刚性。将负责压实的CENP-A结构域替换到组蛋白H3中足以将其引导到着丝粒。因此，CENP-A的着丝粒靶向结构域赋予其组装到其中的核小体独特的结构刚性，并且可能在维持着丝粒身份中起作用。
Mammalian centromeres are not defined by a consensus DNA sequence. In all eukaryotes a hallmark of functional centromeres - both normal ones and those formed aberrantly at atypical loci - is the accumulation of centromere protein A (CENP-A), a histone variant that replaces H3 in centromeric nucleosomes(1-7). Here we show using deuterium exchange/mass spectrometry coupled with hydrodynamic measures that CENP-A and histone H4 form sub-nucleosomal tetramers that are more compact and conformationally more rigid than the corresponding tetramers of histones H3 and H4. Substitution into histone H3 of the domain of CENP-A responsible for compaction is sufficient to direct it to centromeres. Thus, the centromere-targeting domain of CENP-A confers a unique structural rigidity to the nucleosomes into which it assembles, and is likely to have a role in maintaining centromere identity.