Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 43, Pages 33113-33122Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.117044
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- Ministry of Science and Technology of China [2008AA022311, 2010CB944900, 2008AA1011005]
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Nuclear importing system and nuclear factors play important roles in mediating nuclear reprogramming and zygotic gene activation. However, the components and mechanisms that mediate nuclearly specific targeting of the nuclear proteins during nuclear reprogramming and zygotic gene activation remain largely unknown. Here, we identified a novel member of the importin-alpha family, AW146299(KPNA7), which is predominantly expressed in mouse oocytes and zygotes and localizes to the nucleus or spindle. Mutation of Kpna7 gene caused reproductivity reduction and sex imbalance by inducing preferential fetal lethality in females. Parthenogenesis analysis showed that the cell cycle of activated one-cell embryos is loss of control and ahead of schedule but finally failed to develop into blastocyst stage. Further RT-PCR and epigenetic modification analysis showed that knocking out of Kpna7 induced abnormalities of gene expression (dppa2, dppa4, and piwil2) and epigenetic modifications (down-regulation of histone H3K27me3). Biochemical analysis showed that KPNA7 interacts with KPNB1 (importin-beta 1). In summary, we identified a novel Kpna7 gene that is required for normal fertility and fecundity.
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