Dynamics of a novel centromeric histone variant CenH3 reveals the evolutionary ancestral timing of centromere biogenesis
Dynamics of a novel centromeric histone variant CenH3 reveals the evolutionary ancestral timing of centromere biogenesis
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DOI：
10.1093/nar/gkq664
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发表时间：
2010-11-01
影响因子：
14.9
通讯作者：
Nellen, Wolfgang
中科院分区：
文献类型：
--
作者：
Dubin, Manu;Fuchs, Joerg;Nellen, Wolfgang
着丝粒组蛋白H3变体（CenH3）将着丝点定位于着丝粒，从而确保有丝分裂和减数分裂期间染色体的正确分离。该盘基骨柱h3样变异H3v1被鉴定为CenH3同源。Dictyostelium CenH3具有一个与其他已知蛋白不相似的扩展的n端结构域，并在其c端具有组蛋白折叠结构域。在组蛋白折叠中，α -螺旋2 （α 2）和延伸环1 （L1）被证明是将CenH3靶向着丝粒所必需的。与其他已知和推测的CenH3组蛋白相比，Dictyostelium CenH3具有更短的L1，这表明这种延伸不是必需的特征。通过对活细胞和固定细胞的ChIP分析和荧光显微镜观察，我们首次对阿米巴原虫的着丝粒结构进行了研究。发现这6个远心着丝粒大部分由所有DIRS-1元素组成，并与H3K9me3相关。在间期，着丝粒仍然附着在中心体上，形成一个含cenh3的簇。Dictyostelium CenH3在着丝粒上的装载发生在G2/前期，而在后生动物中观察到的CenH3装载发生在后期/末期。这表明，在G2/前期的装载是原始的真核生物机制，而在变形虫从动物谱系分化出来之后，CenH3的后期/末期装载是最近才进化出来的。
The centromeric histone H3 variant (CenH3) serves to target the kinetochore to the centromeres and thus ensures correct chromosome segregation during mitosis and meiosis. The Dictyostelium H3-like variant H3v1 was identified as the CenH3 ortholog. Dictyostelium CenH3 has an extended N-terminal domain with no similarity to any other known proteins and a histone fold domain at its C-terminus. Within the histone fold, alpha-helix 2 (alpha 2) and an extended loop 1 (L1) have been shown to be required for targeting CenH3 to centromeres. Compared to other known and putative CenH3 histones, Dictyostelium CenH3 has a shorter L1, suggesting that the extension is not an obligatory feature. Through ChIP analysis and fluorescence microscopy of live and fixed cells, we provide here the first survey of centromere structure in amoebozoa. The six telocentric centromeres were found to mostly consist of all the DIRS-1 elements and to associate with H3K9me3. During interphase, the centromeres remain attached to the centrosome forming a single CenH3-containing cluster. Loading of Dictyostelium CenH3 onto centromeres occurs at the G2/prophase transition, in contrast to the anaphase/telophase loading of CenH3 observed in metazoans. This suggests that loading during G2/prophase is the ancestral eukaryotic mechanism and that anaphase/telophase loading of CenH3 has evolved more recently after the amoebozoa diverged from the animal linage.