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有读书笔记Helicobacter pylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation

阿平 添加于 2010-1-20 06:37 | 2168 次阅读 | 0 个评论

  •  作 者

    Fehri LF, Rechner C, Janbetaen S, Mak TN, Holland C, Bartfeld S, Bruggemann H, Meyer TF

  •  摘 要

    Post-translational modifications of core histones are important components of the epigenetic landscape. Recent investigations of bacterial or toxin-induced effects on histone phosphorylation and acetylation in host cells have linked the changes to transcriptional alterations of key cellular response pathways. However, these changes may have other reasons and functional consequences. Here, we show that infection of gastric epithelial cell lines with the carcinogenic bacterium Helicobacter pylori leads to changes in histone H3 phosphorylation: type IV secretion system (T4SS)-dependent decreases of H3 phosphorylation levels at serine 10 (pH3Ser10) and threonine 3 (pH3Thr3) were observed. Immunofluorescence experiments with pH3Ser10 and cyclin B1 revealed that a H. pylori-induced transient pre-mitotic arrest was responsible for the observed reduction. This causal link was substantiated further by showing that H. pylori causes a strong decrease of the cell division cycle 25 (CDC25C) phosphatase. As a consequence, mitotic histone H3 kinases such as vaccinia-related kinase 1 (VRK1) and Aurora B were not fully activated in infected cells. We show that VRK1 activity, measured using a kinase activity assay, was reduced after H. pylori infection by approximately 40%. Moreover, overexpression of VRK1, but not Aurora B, compensated for the H. pylori-induced decrease of pH3Ser10. Rephosphorylation of H3Ser10 was IkappaB kinase alpha (IKKalpha)-dependent and occurred at later time points of infection. Taken together, our work highlights the impact of bacterial pathogens on host cell chromatin; this modulation reflects the subversion of key cellular processes such as cell cycle progression.

  •  详细资料

    • 文献种类:期刊
    • 期刊名称: Epigenetics : Official Journal of the DNA Methylation Society
    • 期刊缩写: Epigenetics
    • 期卷页: 2009年  第4卷 第8期
    • 地址: Max Planck Institute for Infection Biology, Department of Molecular Biology, Berlin, Germany
    • ISBN: 1559-2308
    • 备注:PMID:20081355

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  •  标 签

    H3T3  H3S10 

  • 相关链接  URL 

  •  阿平 的文献笔记  订阅

    发现一个幽门螺旋杆菌致胃病机制的表遗传标志

    这篇文章是表遗传指标提示致病性机制很有意思的例子，细菌可以通过Type IV secretion system将DNA或蛋白注入到人体细胞，从而影响正常细胞的biological process，作者观察到这些细胞的H3T3ph和 H3S10ph信号下降，再找对应的激酶，发现VRK1和Aurora B等激酶活性是下降的，再倒推发现是CDC25C水平下降造成细胞无法正常进入mitosis，下游激酶无法完全活化，故而组蛋白磷酸化不充分，才会出现这样的信号改变。

    有意思的是，过表达VRK1可以让H3T3ph恢复正常，而过表达Aurora B却不能逆转前面的H3S10ph信号下降，这个发现很有意思，现在还没有看过全文，到时有机会补充讨论

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