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A Role for RNAi in the Selective Correction of DNA Methylation Defects

机译:RNAi在选择性纠正DNA甲基化缺陷中的作用

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摘要

DNA methylation is essential for silencing transposable elements and some genes in higher eukaryotes, which suggests that this modification must be tightly controlled. However, accidental changes in DNA methylation can be transmitted through mitosis (as in cancer) or meiosis, leading to epiallelic variation. We demonstrated the existence of an efficient mechanism that protects against transgenerational loss of DNA methylation in Arabidopsis. Remethylation is specific to the subset of heavily methylated repeats that are targeted by the RNA interference (RNAi) machinery. This process does not spread into flanking regions, is usually progressive over several generations, and faithfully restores wild-type methylation over target sequences in an RNAi-dependent manner. Our findings suggest an important role for RNAi in protecting genomes against long-term epigenetic defects.
机译:DNA甲基化对于沉默转座因子和高级真核生物中的某些基因必不可少,这表明必须严格控制这种修饰。但是,DNA甲基化的偶然变化可以通过有丝分裂(如在癌症中)或减数分裂传播,从而导致表位变异。我们证明了一种有效的机制可以防止拟南芥中DNA甲基化的跨代丢失。重新甲基化特定于RNA干扰(RNAi)机制靶向的高度甲基化重复序列的子集。该过程不会扩散到侧翼区域,通常经过数代进化,并以RNAi依赖性方式忠实地恢复靶序列上的野生型甲基化。我们的发现表明,RNAi在保护基因组免受长期表观遗传缺陷方面具有重要作用。

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  • 来源
    《Science》 |2009年第5921期|1600-1604|共5页
  • 作者单位

    Unite de Recherche en Genomique Vegetale, CNRS UMR 8114, Institut National de la Recherche Argonomique UMR 1165, Universite d'Evry Val d'Essonne, 91057 Evry Cedex, France CNRS UMR 8186, Departement de Biologie, Ecole Normale Superieure, 75230 Paris Cedex 05, France;

    Unite de Recherche en Genomique Vegetale, CNRS UMR 8114, Institut National de la Recherche Argonomique UMR 1165, Universite d'Evry Val d'Essonne, 91057 Evry Cedex, France;

    CNRS UMR 8186, Departement de Biologie, Ecole Normale Superieure, 75230 Paris Cedex 05, France;

    Unite de Recherche en Genomique Vegetale, CNRS UMR 8114, Institut National de la Recherche Argonomique UMR 1165, Universite d'Evry Val d'Essonne, 91057 Evry Cedex, France CNRS UMR 8186, Departement de Biologie, Ecole Normale Superieure, 75230 Paris Cedex 05, France;

    Unite de Recherche en Genomique Vegetale, CNRS UMR 8114, Institut National de la Recherche Argonomique UMR 1165, Universite d'Evry Val d'Essonne, 91057 Evry Cedex, France CNRS UMR 8186, Departement de Biologie, Ecole Normale Superieure, 75230 Paris Cedex 05, France;

    Institut de Biologie Moleculaire des Plantes, CNRS Unite Propre de Recherche 2357, 67084 Strasbourg Cedex, France CNRS UMR 218, Institut Curie, 75248 Paris Cedex 05, France;

    Genoscope, Commissariat a L'Energie Atomique-Institut de Genomique, 91057 Evry Cedex, France;

    Genoscope, Commissariat a L'Energie Atomique-Institut de Genomique, 91057 Evry Cedex, France;

    Laboratorio de Epigenetica del Cancer, Centre Manorial de Investigationes Oncologicas, 28029 Madrid, Spain;

    Laboratorio de Epigenetica del Cancer, Centre Manorial de Investigationes Oncologicas, 28029 Madrid, Spain;

    Institut de Biologie Moleculaire des Plantes, CNRS Unite Propre de Recherche 2357, 67084 Strasbourg Cedex, France;

    Genoscope, Commissariat a L'Energie Atomique-Institut de Genomique, 91057 Evry Cedex, France;

    Laboratorio de Epigenetica del Cancer, Centre Manorial de Investigationes Oncologicas, 28029 Madrid, Spain;

    Unite de Recherche en Genomique Vegetale, CNRS U;

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