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有读书笔记Protein phosphatase 1 regulates the histone code for long-term memory

阿平 添加于 2009-10-23 07:12 | 2212 次阅读 | 0 个评论

  •  作 者

    Koshibu K, Graff J, Beullens M, Heitz FD, Berchtold D, Russig H, Farinelli M, Bollen M, Mansuy IM

  •  摘 要

    Chromatin remodeling through histone posttranslational modifications (PTMs) and DNA methylation has recently been implicated in cognitive functions, but the mechanisms involved in such epigenetic regulation remain poorly understood. Here, we show that protein phosphatase 1 (PP1) is a critical regulator of chromatin remodeling in the mammalian brain that controls histone PTMs and gene transcription associated with long-term memory. Our data show that PP1 is present at the chromatin in brain cells and interacts with enzymes of the epigenetic machinery including HDAC1 (histone deacetylase 1) and histone demethylase JMJD2A (jumonji domain-containing protein 2A). The selective inhibition of the nuclear pool of PP1 in forebrain neurons in transgenic mice is shown to induce several histone PTMs that include not only phosphorylation but also acetylation and methylation. These PTMs are residue-specific and occur at the promoter of genes important for memory formation like CREB (cAMP response element-binding protein) and NF-kappaB (nuclear factor-kappaB). These histone PTMs further co-occur with selective binding of RNA polymerase II and altered gene transcription, and are associated with improved long-term memory for objects and space. Together, these findings reveal a novel mechanism for the epigenetic control of gene transcription and long-term memory in the adult brain that depends on PP1.

  •  详细资料

    • 文献种类: Journal Article
    • 期刊名称: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
    • 期刊缩写: J Neurosci
    • 期卷页: 2009年  第29卷 第41期 13079-13089页
    • 地址: Brain Research Institute, University of Zurich, Swiss Federal Institute of Technology, CH-8057 Zurich, Switzerland
    • ISBN: 1529-2401
    • 备注:PMID:19828821

  • 学科领域 生物医药 » 生物学

  •  标 签

    PP1  NIPP1 

  • 相关链接 DOI URL 

  •  阿平 的文献笔记  订阅

    这篇文章作者的实验室是和我们的合作伙伴，他们自从上次一篇PP1和I1的故事发到了Nature之后，试图再次尝尝甜头，结果这篇文章投Nature等了3年，最终来来回回还是没有成功，结果发了现在这样一个档次的杂志，唉，世界上不知道有多少人在这样投Nature的途中老去了，甚至死去了，他们的成果也在这个过程中贬值了，还可能被人抢先了。

    Cell，Nature，Science 算不了什么，有多少能得诺贝尔奖的文章会产生在这些大牛杂志里呢？用Google的PR计算，最牛的杂志是JBC，那样的杂志才是孕育新思维的优良胎盘。

    文章我就不评述了，因为此文中的老鼠还在折磨我呢，我必须先征服他们。

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