在基因组中除了DNA和RNA序列以外,还有许多调控基因的信息,它们虽然本身不改变基因的序列,但是可以通过基因修饰,蛋白质与蛋白质、DNA和其它分子的相互作用,而影响和调节遗传的基因的功能和特性,并且通过细胞分裂和增殖周期影响遗传,这就是表观遗传学(epigenetics)。
在表观遗传学研究中,小分子RNAs(Short interfering RNAs,siRNAs)可以引导DNA甲基化,以及异染色质组蛋白修饰,导致序列特异性转录基因沉默。这一路径称为RNA介导的DNA甲基化路径(RNA-directed DNA methylation,简称RdDM)。
在本研究中,研究人员鉴定了一个RdDM的效应器(RdDM effector),KTF1。KTF1发生功能性丧失的突变会导致DNA甲基化程度变小,并释放出沉默RdDM转座子的siRNA,促进沉默RdDM路径。KTF1与转录延伸因子(transcription elongation factor)SPT5相似,其C端富含GWWG重复序列。
KTF1与ARGONAUTE4(AGO4)一起定位在核心位置,并与AGO4和RNA转录因子结合。
研究结果表明,KTF1是一个衔接蛋白,它同时链接AGO4和Pol V产生的转录因子网路,AGO4结合到siRNA,以上的分子结合在一起形成RdDM效应复合物。这种复合效应器的特征是具有双重的结合作用,同时结合AGO4和转录因子。(生物谷Bioon.com)
生物谷推荐原始出处:
Cell, Volume 137,1 May 2009 doi:10.1016/j.cell.2009.04.028
An Effector of RNA-Directed DNA Methylation in Arabidopsis Is an ARGONAUTE 4- and RNA-Binding Protein
Xin-Jian He1,6,Yi-Feng Hsu1,3,6,Shihua Zhu1,4,Andrzej T. Wierzbicki5,Olga Pontes5,Craig S. Pikaard5,Hai-Liang Liu1,Co-Shine Wang3,Hailing Jin2andJian-Kang Zhu1,,
1 Institute for Integrative Genome Biology and Department of Botany and Plant Sciences, University of California, Riverside, Riverside, CA 92521, USA
2 Institute for Integrative Genome Biology and Department of Plant Pathology, University of California, Riverside, Riverside, CA 92521, USA
3 Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan
4 College of Science and Technology, Ningbo University, Ningbo 315211, China
5 Biology Department, Washington University, Campus Box 1137, One Brookings Drive, St. Louis, MO 63130, USA
6 These authors contributed equally to this work
DNA methylation is a conserved epigenetic mark inplants and mammals. In Arabidopsis, DNA methylation can be triggered by small interfering RNAs (siRNAs) through an RNA-directed DNA methylation (RdDM) pathway. Here, we report the identification of an RdDM effector, KTF1. Loss-of-function mutations in KTF1 reduce DNA methylation and release the silencing of RdDM target loci without abolishing the siRNA triggers. KTF1 has similarity to the transcription elongation factor SPT5 and contains a C-terminal extension rich in GW/WG repeats. KTF1 colocalizes with ARGONAUTE 4 (AGO4) in punctate nuclear foci and binds AGO4 and RNA transcripts. Our results suggest KTF1 as an adaptor protein that binds scaffold transcripts generated by Pol V and recruits AGO4 and AGO4-bound siRNAs to form an RdDM effector complex. The dual interaction of an effector protein with AGO and small RNA target transcripts may bea general feature of RNA-silencing effector complexes.