Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
Cell Microbiol. 2012 Sep;14(9):1391-401. doi: 10.1111/j.1462-5822.2012.01803.x. Epub 2012 May 15.
Centromeres are essential for the faithful transmission of chromosomes to the next generation, therefore being essential in all eukaryotic organisms. The centromeres of Plasmodium falciparum, the causative agent of the most severe form of malaria, have been broadly mapped on most chromosomes, but their epigenetic composition remained undefined. Here, we reveal that the centromeric histone variant PfCENH3 occupies a 4-4.5 kb region on each P. falciparum chromosome, which is devoid of pericentric heterochromatin but harbours another histone variant, PfH2A.Z. These CENH3 covered regions pinpoint the exact position of the centromere on all chromosomes and revealed that all centromeric regions have similar size and sequence composition. Immunofluorescence assay of PfCENH3 strongly suggests that P. falciparum centromeres cluster to a single nuclear location prior to and during mitosis and cytokinesis but dissociate soon after invasion. In summary, we reveal a dynamic association of Plasmodium centromeres, which bear a unique epigenetic signature and conform to a strict structure. These findings suggest that DNA-associated and epigenetic elements play an important role in centromere establishment in this important human pathogen.
着丝粒对于将染色体忠实传递到下一代至关重要，因此在所有真核生物中都是必不可少的。疟原虫裂殖体，即最严重疟疾形式的病原体，其着丝粒已在大多数染色体上广泛定位，但它们的表观遗传组成仍未确定。在这里，我们揭示 PfCENH3 着丝粒组蛋白变体占据每个 P. falciparum 染色体上的 4-4.5 kb 区域，该区域缺乏着丝粒异染色质，但含有另一种组蛋白变体 PfH2A.Z。这些 CENH3 覆盖区域精确地标定了所有染色体着丝粒的位置，并表明所有着丝粒区域具有相似的大小和序列组成。PfCENH3 的免疫荧光分析强烈表明，裂殖体在有丝分裂和胞质分裂之前和期间聚集到单个核位置，但在入侵后很快就会分离。总之，我们揭示了疟原虫着丝粒的动态关联，这些着丝粒具有独特的表观遗传特征，并符合严格的结构。这些发现表明，在这种重要的人类病原体中，DNA 相关和表观遗传元件在着丝粒的建立中发挥着重要作用。
