Kim Daniel H, Villeneuve Louisa M, Morris Kevin V, Rossi John J
Graduate School of Biological Sciences, Beckman Research Institute of the City of Hope, 1450 E. Duarte Road, Duarte, California 91010, USA.
Nat Struct Mol Biol. 2006 Sep;13(9):793-7. doi: 10.1038/nsmb1142. Epub 2006 Aug 27.
Argonaute proteins are the core components of effector complexes that facilitate RNA interference (RNAi). Small interfering RNAs (siRNAs) targeted to promoter regions mediate transcriptional gene silencing (TGS) in human cells through heterochromatin formation. RNAi effector complexes have yet to be implicated in the mechanism of mammalian TGS. Here we describe the role of the human Argonaute-1 homolog (AGO1) in directing TGS at the promoters for human immunodeficiency virus-1 coreceptor CCR5 and tumor suppressor RASSF1A. AGO1 associates with RNA polymerase II (RNAPII) and is required for histone H3 Lys9 dimethylation and TGS. AGO1, TAR RNA-binding protein-2 (7TRBP2) and Polycomb protein EZH2 colocalize to the siRNA-targeted RASSF1A promoter, implicating Polycomb silencing in the mechanism of mammalian TGS. These results establish a connection between RNAi components AGO1 and TRBP2, RNAPII transcription and Polycomb-regulated control of gene expression.
AGO蛋白是促进RNA干扰（RNAi）的效应复合物的核心组分。靶向启动子区域的小干扰RNA（siRNA）通过异染色质形成介导人类细胞中的转录基因沉默（TGS）。RNAi效应复合物尚未涉及哺乳动物TGS的机制。在此我们描述了人类AGO1同源物（AGO1）在指导针对人类免疫缺陷病毒1型共受体CCR5和肿瘤抑制因子RASSF1A启动子的TGS中的作用。AGO1与RNA聚合酶II（RNAPII）相关联，并且是组蛋白H3赖氨酸9二甲基化和TGS所必需的。AGO1、TAR RNA结合蛋白2（TRBP2）和多梳蛋白EZH2共定位于siRNA靶向的RASSF1A启动子，表明多梳沉默参与哺乳动物TGS机制。这些结果建立了RNAi组分AGO1和TRBP2、RNAPII转录与多梳调控的基因表达控制之间的联系。
