Influence of DNA methylation on positioning and DNA flexibility of nucleosomes with pericentric satellite DNA.
Influence of DNA methylation on positioning and DNA flexibility of nucleosomes with pericentric satellite DNA.
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DOI：
10.1098/rsob.150128
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发表时间：
2015-10
期刊：
影响因子：
5.8
通讯作者：
Kurumizaka H
中科院分区：
文献类型：
--
作者：
Osakabe A;Adachi F;Arimura Y;Maehara K;Ohkawa Y;Kurumizaka H
DNA甲基化发生在CpG位点上，对形成中心周围异染色质结构域很重要。卫星2序列包含7个CpG位点，位于人类1号染色体的中心周围区域，在正常细胞中高度甲基化。相反，据报道，在癌细胞中卫星2区是低甲基化的，这表明甲基化状态可能影响肿瘤中中心周围区域的染色质结构。在这项研究中，我们在体外绘制了卫星2序列上的核小体定位，发现DNA甲基化对核小体定位的分布有轻微的影响。微球菌核酸酶测定显示，核小体的DNA末端灵活性的变化，取决于DNA甲基化状态。然而，核小体的结构和热稳定性不受DNA甲基化的影响。这些发现为理解DNA甲基化如何在正常和恶性细胞中调节中心周围异染色质的形成和维持提供了新的信息。
DNA methylation occurs on CpG sites and is important to form pericentric heterochromatin domains. The satellite 2 sequence, containing seven CpG sites, is located in the pericentric region of human chromosome 1 and is highly methylated in normal cells. In contrast, the satellite 2 region is reportedly hypomethylated in cancer cells, suggesting that the methylation status may affect the chromatin structure around the pericentric regions in tumours. In this study, we mapped the nucleosome positioning on the satellite 2 sequence in vitro and found that DNA methylation modestly affects the distribution of the nucleosome positioning. The micrococcal nuclease assay revealed that the DNA end flexibility of the nucleosomes changes, depending on the DNA methylation status. However, the structures and thermal stabilities of the nucleosomes are unaffected by DNA methylation. These findings provide new information to understand how DNA methylation functions in regulating pericentric heterochromatin formation and maintenance in normal and malignant cells.