美国NIH旗下国立衰老研究所，韩国Gyeongsang National大学兽医学院的科学家发现Zscan4蛋白对小鼠胚胎干细胞的基因组稳定性有关键调控作用，相关成果文章Zscan4 regulates telomere elongation and genomic stability in ES cells公布在*新一期的Nature上。 万事万物都处于运动当中，细胞中的基因组也不例外，基因组可能发生突变，可能发生序列重复，种种的变故导致基因组重排和不稳定。一旦，这些细微的变化蓄积的多了，或是在某些关键的部分发生决定性的变化可能导致机体机能发生变化，导致**甚至癌症的发生。
在每个细胞中，有大量的不同的蛋白保护着基因组，维持基因组的稳定性，防止重排或是错配的发生。但是，究竟是哪些蛋白，哪些基因在这过程中发挥了重要的作用，科学家们并不清楚。
小鼠胚胎干细胞（ES细胞）在培养细胞中以基因组稳定性知名，能够在不失去其正常染色体组型（核型）的条件下长期保持存活。
研究小组发现，Zscan4蛋白被发现有助于维持这些细胞中的端粒和基因组稳定性。ES细胞只有5%在任何时候都表达Zscan4，但几乎所有ES细胞在九次通过中都至少激发Zscan4一次。瞬间的Zscan4-阳性状态与由端粒重组和减数分裂特异性同源重组基因的上调所引起的快速端粒延伸相联系。这个发现提出一个可能性：促进Zscan4表达也许可提高干细胞或癌细胞等其他细胞类型中的基因组稳定性。
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Nature 464, 858-863 (8 April 2010) |doi:10.1038/nature08882; Received 29 June 2009; Accepted 8 February2010; Published online 24 March 2010
Zscan4 regulates telomere elongation andgenomic stability in ES cells
Michal Zalzman1, Geppino Falco1,3,Lioudmila V. Sharova1, Akira Nishiyama1, Marshall Thomas1, Sung-LimLee1,3, Carole A. Stagg1, Hien G. Hoang1, Hsih-Te Yang1, Fred E.Indig2, Robert P. Wersto2 & Minoru S. H. Ko1
Developmental Genomics and Aging Section,Laboratory of Genetics,
Research Resources Branch, NationalInstitute on Aging, NIH, Baltimore, Maryland 21224,USA
Present addresses: Istituto di RicercheGenetiche Gaetano Salvatore Biogem s.c.ar.l., Ariano Irpino 83031,Italy (G.F.); College of Veterinary Medicine, Gyeongsang NationalUniversity, Jinju, Gyeongnam 660701, Republic of Korea(S.-L.L.).
Correspondence to: Minoru S. H. Ko1Correspondence and requests for materials should be addressed toM.S.H.K. (Email: kom@mail.nih.gov).
【Abstract】
Exceptional genomic stability is one ofthe hallmarks of mouse embryonic stem (ES) cells. However, thegenes contributing to this stability remain obscure. We previouslyidentified Zscan4 as a specific marker for two-cell embryo and EScells. Here we show that Zscan4 is involved in telomere maintenanceand long-term genomic stability in ES cells. Only 5% of ES cellsexpress Zscan4 at a given time, but nearly all ES cells activateZscan4 at least once during nine passages. The transientZscan4-positive state is associated with rapid telomere extensionby telomere recombination and upregulation of meiosis-specifichomologous recombination genes, which encode proteins that arecolocalized with ZSCAN4 on telomeres. Furthermore, Zscan4 knockdownshortens telomeres, increases karyotype abnormalities andspontaneous sister chromatid exchange, and slows down cellproliferation until reaching crisis by passage eight. Together, ourdata show a unique mode of genome maintenance in EScells.