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, Minoru Ko

Research output: Contribution to journalArticle

189 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)858-863
Number of pages6
JournalNature
Volume464
Issue number7290
DOIs
Publication statusPublished - 2010 Apr 8
Externally publishedYes

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Genomic Instability
Telomere
Embryonic Stem Cells
Maintenance
Telomere Shortening
Sister Chromatid Exchange
Homologous Recombination
Meiosis
Karyotype
Genetic Recombination
Genes
Up-Regulation
Embryonic Structures
Cell Proliferation
Genome
Proteins

ASJC Scopus subject areas

  • General

Cite this

Zalzman, M., Falco, G., Sharova, L. V., Nishiyama, A., Thomas, M., Lee, S. L., ... Ko, M. (2010). Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature, 464(7290), 858-863. https://doi.org/10.1038/nature08882

Zscan4 regulates telomere elongation and genomic stability in ES cells. / Zalzman, Michal; Falco, Geppino; Sharova, Lioudmila V.; Nishiyama, Akira; Thomas, Marshall; Lee, Sung Lim; Stagg, Carole A.; Hoang, Hien G.; Yang, Hsih Te; Indig, Fred E.; Wersto, Robert P.; Ko, Minoru.

In: Nature, Vol. 464, No. 7290, 08.04.2010, p. 858-863.

Research output: Contribution to journalArticle

Zalzman, M, Falco, G, Sharova, LV, Nishiyama, A, Thomas, M, Lee, SL, Stagg, CA, Hoang, HG, Yang, HT, Indig, FE, Wersto, RP & Ko, M 2010, 'Zscan4 regulates telomere elongation and genomic stability in ES cells', Nature, vol. 464, no. 7290, pp. 858-863. https://doi.org/10.1038/nature08882
Zalzman M, Falco G, Sharova LV, Nishiyama A, Thomas M, Lee SL et al. Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature. 2010 Apr 8;464(7290):858-863. https://doi.org/10.1038/nature08882
Zalzman, Michal ; Falco, Geppino ; Sharova, Lioudmila V. ; Nishiyama, Akira ; Thomas, Marshall ; Lee, Sung Lim ; Stagg, Carole A. ; Hoang, Hien G. ; Yang, Hsih Te ; Indig, Fred E. ; Wersto, Robert P. ; Ko, Minoru. / Zscan4 regulates telomere elongation and genomic stability in ES cells. In: Nature. 2010 ; Vol. 464, No. 7290. pp. 858-863.
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