拟南芥Argonaute1在细胞核内调控基因表达的机制

项目名称： 拟南芥Argonaute1在细胞核内调控基因表达的机制

项目编号： No.31330042

项目类型： 重点项目

立项/批准年度： 2014

项目学科： 遗传学与生物信息学、细胞生物学

项目作者： 戚益军

作者单位： 清华大学

项目金额： 301万元

中文摘要： Argonuate (AGO)家族蛋白作为RNAi通路中的效应蛋白，可特异性地结合各种小RNA，在转录或转录后水平调节基因表达。最近也有研究表明，一些AGO蛋白除了在典型的RNAi通路中的作用外，还可以通过其它机制调节基因表达。拟南芥AGO1主要在细胞质中结合miRNA并以切割靶mRNA的方式调节基因表达。然而，我们发现也有相当一部分AGO1蛋白位于细胞核中，这意味着AGO1可能还在细胞核内另有功能。用ChIP-seq的方法，我们发现AGO1可特异性地结合到1858染色质位点。其中部分靶基因的表达水平在ago1的突变体中有显著的上升，这表明AGO1可以结合特定染色质靶位点，并调节基因表达。本项目拟在此发现的基础上，深入研究拟南芥AGO1结合染色质并调节靶基因表达的作用机制。本项目的研究将有望揭示AGO1调节基因表达的新机制，拓宽和加深我们对植物AGO家族蛋白功能的认识。

中文关键词： 拟南芥;Argonaute蛋白;染色质重塑;小RNA;基因表达调控

英文摘要： As effectors in the RNAi pathway, Argonaute (AGO) family proteins bind to small RNAs, to regulate gene expression at transcriptional or post-transcriptional levels. Some recent studies have shown that in addition to their roles in the RNAi pathway, some AGOs can also modulate gene expression through several other mechanisms. Arabidopsis AGO1 is known to bind to miRNAs and cleave target mRNA in the cytoplasm. However, we found that a considerable amount of AGO1 is also present in the nucleus. Using ChIP-seq analysis, we identified 1,858 AGO1 binding sites in the Arabidopsis genome. Furthermore, we found that the expression of some AGO1 target loci is de-repressed in an ago1 mutant, indicating that AGO1 can bind to specific chromatin sites and regulate their expression. In this project, we aim to dissect the mechanisms through which AGO1 binds to chromatin, and we will also study how AGO1 regulates the expression of the target loci. Results from this project will reveal an unsuspected role for AGO1 in regulating gene expression the nucleus and the mechanisms underlying such regulation. This will also provide novel general insights into the functions of AGO family proteins.

英文关键词： Arabidopsis;Argonaute protein;Chromatin remodeling;small RNA;Regulation of gene expression