Phosphorylation of histone H3 serine 10 in early mouse embryos: Active phosphorylation at late S phase and differential effects of ZM447439 on first two embryonic

Department of Embryology, Institute of Zoology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
Cell cycle (Georgetown, Tex.) (Impact Factor: 4.57). 12/2010; 9(23):4674-87. DOI: 10.4161/cc.9.23.14023
Source: PubMed


Cell division in mammalian cells is regulated by Aurora kinases. The activity of Aurora A is indispensable for correct function of centrosomes and proper spindle formation, while Aurora B for chromosome biorientation and separation. Aurora B is also responsible for the phosphorylation of histone H3 serine 10 (H3S10Ph) from G2 to metaphase. Data concerning the Aurora B activity and H3S10Ph in embryonic cells are limited to primordial and maturing oocytes and advanced pronuclei in zygotes. In the present study we have analyzed H3S10Ph in 1- and 2-cell mouse embryos. We show that H3S10 remains phosphorylated at anaphase and telophase of the second meiotic division, as well as during the anaphase and telophase of the first and second embryonic mitoses. At late G1 H3S10 is dephosphorylated and subsequently phosphorylated de novo at late S phase of the first and second cell cycle. These results show that the H3S10 phosphorylation/dephosphorylation cycle in embryonic cells is different than in somatic cells. The behaviour of thymocyte G0 nuclei introduced into ovulated oocytes and early 1-cell parthenogenotes confirms that kinases responsible for de novo H3S10 phosphorylation, most probably Aurora B, are active until G1 of the first cell cycle of mouse embryo. The inhibition of Aurora kinases by ZM447439 caused abnormalities both in the first and second mitoses. However, the disturbances in each division differed, suggesting important differences in the control of these mitoses. In ZM447439-treated mitotic zygotes Mad2 protein remained continuously present on kinetochores, what confirmed that spindle checkpoint remained active.

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    • "During interphase , binding of HP1 to di-or trimethylated H3K9 maintains a constitutive heterochromatin status. When cells enter mitosis, however, phosphorylation of H3S10, acetylation of H3K14, and possibly methylation of H3K4, hinder methylation of H3K9, causing HP1 to be released from the histone (Fischle et al., 2005; Hirota et al., 2005; Teperek-Tkacz et al., 2010), bringing a change to the higher structure of chromatin. This mechanism , which appears to be fundamental to the role of H3S10 phosphorylation in chromosome condensation during mitosis, has been suggested to apply as well to H3S10 phosphorylation in the promoters of certain genes to regulate transcription during interphase (Winter et al., 2008). "
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    • "For this purpose, embryos were obtained from superovulated F1(C57BL/6xCBA/Tar) females mated with F1 males and the timing of each cell cycle progression was estimated based on the time that passed from hCG injection (in hours post hCG). Such precise timing for this particular strain of mice has been established previously (Teperek-Tkacz et al., 2010) and confirmed (Meglicki et al., 2012). To exclude possible artifacts resulting from using a different mouse strain or a different method of obtaining embryos, we first determined whether localization of LIN28 in embryos derived from superovulated F1 and spontaneously ovulated CD1 mice was similar. "
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    • "Some research groups have investigated this epigenetic modification during early mouse embryogenesis. Their reports suggest that H3S10P is linked to pericentromeric heterochromatin (Huang et al., 2007; Teperek-Tkacz et al., 2010; Wang et al., 2006). Recently, we have shown by immunofluorescence in situ hybridization (immuno-FISH) using specific pericentromeric heterochromatin probes that H3S10P indeed marks constitutive heterochromatin during interphase until the four-cell stage in mouse embryos (Ribeiro-Mason et al., submitted). "
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