Institute for Integrative Genome Biology and Department of Botany and Plant Sciences, University of California, Riverside, California 92521, USA.
Nature. 2010 May 6;465(7294):106-9. doi: 10.1038/nature09025. Epub 2010 Apr 21.
DNA methylation is an important epigenetic mark in many eukaryotes. In plants, 24-nucleotide small interfering RNAs (siRNAs) bound to the effector protein, Argonaute 4 (AGO4), can direct de novo DNA methylation by the methyltransferase DRM2 (refs 2, 4-6). Here we report a new regulator of RNA-directed DNA methylation (RdDM) in Arabidopsis: RDM1. Loss-of-function mutations in the RDM1 gene impair the accumulation of 24-nucleotide siRNAs, reduce DNA methylation, and release transcriptional gene silencing at RdDM target loci. RDM1 encodes a small protein that seems to bind single-stranded methyl DNA, and associates and co-localizes with RNA polymerase II (Pol II, also known as NRPB), AGO4 and DRM2 in the nucleus. Our results indicate that RDM1 is a component of the RdDM effector complex and may have a role in linking siRNA production with pre-existing or de novo cytosine methylation. Our results also indicate that, although RDM1 and Pol V (also known as NRPE) may function together at some RdDM target sites in the peri-nucleolar siRNA processing centre, Pol II rather than Pol V is associated with the RdDM effector complex at target sites in the nucleoplasm.
DNA 甲基化是许多真核生物中重要的表观遗传标记。在植物中，24 核苷酸的小干扰 RNA（siRNA）与效应蛋白 Argonaute 4（AGO4）结合，可以通过甲基转移酶 DRM2（参考文献 2、4-6）直接指导新的 DNA 甲基化。在这里，我们报告了拟南芥中 RNA 指导的 DNA 甲基化（RdDM）的一个新调节剂：RDM1。RDM1 基因的功能丧失突变会损害 24 核苷酸 siRNA 的积累，降低 DNA 甲基化，并在 RdDM 靶标位点释放转录基因沉默。RDM1 编码一种小蛋白，似乎可以结合单链甲基化 DNA，并与核内的 RNA 聚合酶 II（也称为 NRPB）、AGO4 和 DRM2 结合和共定位。我们的结果表明，RDM1 是 RdDM 效应复合物的一个组成部分，可能在将 siRNA 产生与预先存在的或新的胞嘧啶甲基化联系起来方面发挥作用。我们的结果还表明，尽管 RDM1 和 Pol V（也称为 NRPE）可能在核仁周围 siRNA 加工中心的某些 RdDM 靶位点一起发挥作用，但 Pol II 而不是 Pol V 与核质中的 RdDM 效应复合物相关联在靶位点。
