The DNA demethylase ROS1 targets genomic regions with distinct chromatin modifications.

The DNA demethylase ROS1 targets genomic regions with distinct chromatin modifications.
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DOI:
10.1038/nplants.2016.169
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发表时间:
2016-10-31
期刊:
影响因子:
18
通讯作者:
--
中科院分区:
生物学1区
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--
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拟南芥ROS 1/DEMETER 5 mC DNA糖基化酶家族是真核生物中第一个具有遗传特征的DNA去甲基化酶。然而,ROS 1靶向基因组位点的特征还没有很好地理解。在这项研究中,我们的特点是在拟南芥Col-0和C24生态型的ROS 1靶位点。我们发现ROS 1优先靶向转座因子(TEs)和基因间区域。与大多数TE相比,ROS 1靶向的TE更接近蛋白质编码基因,这表明ROS 1可以阻止DNA甲基化从TE扩散到附近的基因。靶向ROS 1的TE特异性富集H3 K18 Ac和H3 K27 me 3,并且耗尽H3 K27 me和H3 K9 me 2。重要的是,我们发现了数千个以前未知的RNA介导的DNA甲基化(RdDM)靶点,这表明ROS 1在这些位点强烈拮抗RdDM。此外,我们还发现ROS 1在某些位点也拮抗RdDM独立的DNA甲基化。我们的研究结果提供了重要的见解ROS 1的全基因组靶点和DNA甲基化和ROS 1介导的主动DNA去甲基化之间的串扰。
The Arabidopsis ROS1/DEMETER family of 5mC DNA glycosylases are the first genetically characterized DNA demethylases in eukaryotes. However, the features of ROS1 targeted genomic loci are not well-understood. In this study, we characterized ROS1 target loci in Arabidopsis Col-0 and C24 ecotypes. We found that ROS1 preferentially targets transposable elements (TEs) and intergenic regions. Compared to most TEs, ROS1-targeted TEs are closer to protein coding genes, suggesting that ROS1 may prevent DNA methylation spreading from TEs to nearby genes. ROS1-targeted TEs are specifically enriched for H3K18Ac and H3K27me3, and depleted of H3K27me and H3K9me2. Importantly, we identified thousands of previously unknown RNA-directed DNA methylation (RdDM) targets upon depletion of ROS1, suggesting that ROS1 strongly antagonizes RdDM at these loci. In addition, we show that ROS1 also antagonizes RdDM-independent DNA methylation at some loci. Our results provide important insights into the genome-wide targets of ROS1 and the crosstalk between DNA methylation and ROS1-mediated active DNA demethylation.
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