| Zscan4 regulates telomere elongation and genomic stability in ES cells. | |
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MedLine Citation:
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PMID: 20336070 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 S H Ko |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2010-03-24 |
Journal Detail:
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Title: Nature Volume: 464 ISSN: 1476-4687 ISO Abbreviation: Nature Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-08 Completed Date: 2010-05-17 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: England |
Other Details:
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Languages: eng Pagination: 858-63 Citation Subset: IM |
Affiliation:
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Developmental Genomics and Aging Section, Laboratory of Genetics, NIH, Baltimore, Maryland 21224, USA |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Line Cell Proliferation Chromosome Aberrations Embryonic Stem Cells / cytology, metabolism*, pathology Gene Expression Regulation Gene Knockdown Techniques Genomic Instability* Karyotyping Meiosis / genetics, physiology Mice Protein Transport Recombination, Genetic / genetics Sister Chromatid Exchange / genetics Telomere / genetics*, metabolism* Transcription Factors / deficiency, genetics, metabolism* Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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ZIA AG000655-11/AG/NIA NIH HHS; ZIA AG000656-11/AG/NIA NIH HHS; ZIA AG000700-02/AG/NIA NIH HHS; ZIA AG000706-02/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Transcription Factors; 0/Zscan4d protein, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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