Zscan4 regulates telomere elongation and genomic stability in ES cells

Michal Zalzman, Geppino Falco, Lioudmila V. Sharova, Akira Nishiyama, Marshall Thomas, Sung-Lim Lee, Carole A. Stagg, Hien G. Hoang, Hsih-Te Yang, Fred E. Indig, Robert P. Wersto and Minoru S. H. Ko ()
Additional contact information
Michal Zalzman: Developmental Genomics and Aging Section, Laboratory of Genetics,
Geppino Falco: Developmental Genomics and Aging Section, Laboratory of Genetics,
Lioudmila V. Sharova: Developmental Genomics and Aging Section, Laboratory of Genetics,
Akira Nishiyama: Developmental Genomics and Aging Section, Laboratory of Genetics,
Marshall Thomas: Developmental Genomics and Aging Section, Laboratory of Genetics,
Sung-Lim Lee: Developmental Genomics and Aging Section, Laboratory of Genetics,
Carole A. Stagg: Developmental Genomics and Aging Section, Laboratory of Genetics,
Hien G. Hoang: Developmental Genomics and Aging Section, Laboratory of Genetics,
Hsih-Te Yang: Developmental Genomics and Aging Section, Laboratory of Genetics,
Fred E. Indig: Research Resources Branch, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA
Robert P. Wersto: Research Resources Branch, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA
Minoru S. H. Ko: Developmental Genomics and Aging Section, Laboratory of Genetics,

Nature, 2010, vol. 464, issue 7290, 858-863

Abstract: Abstract 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.

Date: 2010
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DOI: 10.1038/nature08882

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