Developmental Genomics and Aging Section, Laboratory of Genetics, NIH, Baltimore, Maryland 21224, USA
Nature. 2010 Apr 8;464(7290):858-63. doi: 10.1038/nature08882. Epub 2010 Mar 24.
Exceptional genomic stability is one of the hallmarks of mouse embryonic stem (ES) cells. However, the genes contributing to this stability remain obscure. We previously identified Zscan4 as a specific marker for two-cell embryo and ES cells. Here we show that Zscan4 is involved in telomere maintenance and long-term genomic stability in ES cells. Only 5% of ES cells express Zscan4 at a given time, but nearly all ES cells activate Zscan4 at least once during nine passages. The transient Zscan4-positive state is associated with rapid telomere extension by telomere recombination and upregulation of meiosis-specific homologous recombination genes, which encode proteins that are colocalized with ZSCAN4 on telomeres. Furthermore, Zscan4 knockdown shortens telomeres, increases karyotype abnormalities and spontaneous sister chromatid exchange, and slows down cell proliferation until reaching crisis by passage eight. Together, our data show a unique mode of genome maintenance in ES cells.
胚胎干细胞（ES 细胞）的一个显著特征是具有出色的基因组稳定性。然而，促成这种稳定性的基因仍不明确。我们先前发现 Zscan4 是二细胞胚胎和 ES 细胞的特异性标志物。在这里，我们表明 Zscan4 参与 ES 细胞中端粒维持和长期基因组稳定性。在给定的时间内，只有 5%的 ES 细胞表达 Zscan4，但在九次传代过程中，几乎所有 ES 细胞都会至少激活一次 Zscan4。短暂的 Zscan4 阳性状态与端粒重组导致的端粒快速延伸以及减数分裂特异性同源重组基因的上调有关，这些基因编码的蛋白质与端粒上的 ZSCAN4 共定位。此外，Zscan4 的敲低会缩短端粒，增加染色体异常和自发的姐妹染色单体交换，并减缓细胞增殖，直到在传代 8 时达到危机。总之，我们的数据显示了 ES 细胞中独特的基因组维持模式。
