The SET domain proteins SUVH2 and SUVH9 are required for Pol V occupancy at RNA-directed DNA methylation loci.
The SET domain proteins SUVH2 and SUVH9 are required for Pol V occupancy at RNA-directed DNA methylation loci.
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DOI：
10.1371/journal.pgen.1003948
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发表时间：
2014-01
期刊：
影响因子：
4.5
通讯作者：
He XJ
中科院分区：
文献类型：
--
作者：
Liu ZW;Shao CR;Zhang CJ;Zhou JX;Zhang SW;Li L;Chen S;Huang HW;Cai T;He XJ
RNA指导的DNA甲基化（RdDM）是拟南芥中转座子和其他DNA重复序列转录沉默所必需的。尽管先前的研究已经证明含有SET结构域的SU（VAR）3-9同源物SUVH 2和SUVH 9参与RdDM途径，但其潜在机制仍然未知。我们的研究结果表明，SUV H2和/或SUV H9不仅与称为DDR（DMS 3，DRD 1和RDM 1）的染色质重塑复合物相互作用，而且还与由两个保守的Microrchidia（MORC）家族蛋白MORC 1和MORC 6组成的新特征复合物相互作用。suvh 2suvh 9对Pol IV依赖性siRNA积累和DNA甲基化的作用与Pol V突变体nrpe 1和DDR复合物突变体dms 3的作用相当，表明SUV H2和SUV H9在功能上与RdDM相关。我们的CHIP测定表明，SUV H2和SUV H9是在RdDM基因座处占据Pol V所必需的，并且促进Pol V依赖性非编码RNA的产生。此外，SUV H2和SUV H9还参与了RdDM基因座上DMS 3的占据。推测SUV H2的SET结构域中的催化活性位点是SUV H2在RdDM和H3 K9二甲基化中的功能的基础。我们提出，SUV H2和SUV H9结合到甲基化的DNA，并通过与DDR复合物和MORC复合物相关联来促进Pol V向RdDM基因座的募集。在植物、真菌和动物中，小RNA诱导的转座元件和其他DNA重复序列的转录沉默是一种进化上保守的机制。在拟南芥中，RNA指导的DNA甲基化途径参与转录沉默。由植物特异性DNA依赖性RNA聚合酶V产生的非编码RNA是RNA指导的DNA甲基化所必需的。染色质重塑复合物先前被证明是所需的DNA依赖的RNA聚合酶V在RNA指导的DNA甲基化位点的占用。我们的研究结果表明，两个假定的组蛋白甲基转移酶在其酶活性是无活性的，并作为衔接蛋白，以促进招聘的DNA依赖的RNA聚合酶V染色质与染色质重塑复合物。结合以前的研究，我们提出，无活性的组蛋白甲基转移酶结合到甲基化的DNA，从而连接DNA甲基化的RNA指导的DNA甲基化位点的Pol V转录。
RNA-directed DNA methylation (RdDM) is required for transcriptional silencing of transposons and other DNA repeats in Arabidopsis thaliana. Although previous research has demonstrated that the SET domain-containing SU(VAR)3–9 homologs SUVH2 and SUVH9 are involved in the RdDM pathway, the underlying mechanism remains unknown. Our results indicated that SUVH2 and/or SUVH9 not only interact with the chromatin-remodeling complex termed DDR (DMS3, DRD1, and RDM1) but also with the newly characterized complex composed of two conserved Microrchidia (MORC) family proteins, MORC1 and MORC6. The effect of suvh2suvh9 on Pol IV-dependent siRNA accumulation and DNA methylation is comparable to that of the Pol V mutant nrpe1 and the DDR complex mutant dms3, suggesting that SUVH2 and SUVH9 are functionally associated with RdDM. Our CHIP assay demonstrated that SUVH2 and SUVH9 are required for the occupancy of Pol V at RdDM loci and facilitate the production of Pol V-dependent noncoding RNAs. Moreover, SUVH2 and SUVH9 are also involved in the occupancy of DMS3 at RdDM loci. The putative catalytic active site in the SET domain of SUVH2 is dispensable for the function of SUVH2 in RdDM and H3K9 dimethylation. We propose that SUVH2 and SUVH9 bind to methylated DNA and facilitate the recruitment of Pol V to RdDM loci by associating with the DDR complex and the MORC complex. Small RNA-induced transcriptional silencing at transposable elements and other DNA repeats is an evolutionarily conserved mechanism in plants, fungi, and animals. In Arabidopsis thaliana, an RNA-directed DNA methylation pathway is involved in transcriptional silencing. Noncoding RNAs produced by the plant-specific DNA-dependent RNA polymerase V are required for RNA-directed DNA methylation. A chromatin-remodeling complex was previously demonstrated to be required for the occupancy of DNA-dependent RNA polymerase V at RNA-directed DNA methylation loci. Our results suggest that two putative histone methyltransferases are inactive in their enzymatic activity and act as adaptor proteins to facilitate the recruitment of DNA-dependent RNA polymerase V to chromatin by associating with the chromatin-remodeling complex. In combination with previous studies, we propose that the inactive histone methyltransferases bind to methylated DNA, thereby linking DNA methylation to Pol V transcription at RNA-directed DNA methylation loci.
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影响因子：
4.5
作者：
Johnson LM;Law JA;Khattar A;Henderson IR;Jacobsen SE
通讯作者：
Jacobsen SE
DOI：
10.1038/nrg3355
发表时间：
2013-02
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.5
作者：
Henderson IR;Deleris A;Wong W;Zhong X;Chin HG;Horwitz GA;Kelly KA;Pradhan S;Jacobsen SE
通讯作者：
Jacobsen SE
影响因子：
64.8
作者：
Ito, Hidetaka;Gaubert, Herve;Paszkowski, Jerzy
通讯作者：
Paszkowski, Jerzy
影响因子：
64.8
作者：
Jackson, JP;Lindroth, AM;Jacobsen, SE
通讯作者：
Jacobsen, SE