Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana.
Interplay between active chromatin marks and RNA-directed DNA methylation in Arabidopsis thaliana.
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DOI：
10.1371/journal.pgen.1003946
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发表时间：
2013-11
期刊：
影响因子：
4.5
通讯作者：
Jacobsen SE
中科院分区：
文献类型：
--
作者：
Greenberg MV;Deleris A;Hale CJ;Liu A;Feng S;Jacobsen SE
DNA甲基化是一种表观遗传标记，与转座因子和蛋白质编码基因的转录抑制有关。相反，转录活性调控区与组蛋白3赖氨酸4二-和三甲基化（H3 K4 m2/m3）密切相关。我们先前表明，具有H3 K4 m2/m3去甲基化酶JUMONJI 14（JMJ 14）突变的拟南芥植物表现出与H3 K4 m2/m3水平增加相关的RNA指导的DNA甲基化（RdDM）的轻度减少。为了确定这种不完全的RdDM减少是否是与其他脱甲基酶冗余的结果，我们检查了JMJ 14与另一类H3 K4脱甲基酶的遗传相互作用：赖氨酸特异性脱甲基酶1样1和赖氨酸特异性脱甲基酶1样2（LDL 1和LDL 2）。全基因组DNA甲基化分析表明，这两个家庭合作，以维持RdDM模式。ChIP-seq实验表明，表现出可观察到的DNA甲基化降低的区域与H3 K4 m2/m3的增加是偶然的。有趣的是，对DNA甲基化的影响在邻近H3 K4 m2/m3标记的蛋白质编码基因的DNA甲基化区域更强，这表明H3 K4去甲基化酶的活性可能对防止活性表观遗传标记的传播特别重要。最后，RNA测序分析表明，在RdDM靶点，H3 K4 m2/m3的增加通常与转录去抑制无关。这表明组蛋白标记本身-而不是转录-影响RdDM的程度。许多因素有助于真核生物基因组的组织和基础基因的表达状态。例如，胞嘧啶碱基可以通过添加甲基基团来修饰。在模式植物拟南芥中，甲基化的胞嘧啶通常与转录抑制区域-所谓的“异染色质”相关。此外，基因组DNA包裹在核小体周围;每个核小体由八个组蛋白组成的复合物组成。反过来，组蛋白上的氨基酸残基可以通过多种方式进行修饰，其中之一是甲基化。组蛋白3（H3 K4）赖氨酸4上的甲基修饰与转录激活相关。拟南芥全基因组研究表明，DNA甲基化和H3 K4甲基化高度反相关。在本文中，我们研究了一组拟南芥突变体，其中H3 K4甲基化在基因组中的一些位点异常高。在这些基因座中的几个，DNA甲基化水平在相同的突变体中降低。这些数据表明，H3 K4甲基化拮抗DNA甲基化，这可能有助于区分基因组的活性区域和沉默区域的机制。
DNA methylation is an epigenetic mark that is associated with transcriptional repression of transposable elements and protein-coding genes. Conversely, transcriptionally active regulatory regions are strongly correlated with histone 3 lysine 4 di- and trimethylation (H3K4m2/m3). We previously showed that Arabidopsis thaliana plants with mutations in the H3K4m2/m3 demethylase JUMONJI 14 (JMJ14) exhibit a mild reduction in RNA-directed DNA methylation (RdDM) that is associated with an increase in H3K4m2/m3 levels. To determine whether this incomplete RdDM reduction was the result of redundancy with other demethylases, we examined the genetic interaction of JMJ14 with another class of H3K4 demethylases: LYSINE-SPECIFIC DEMETHYLASE 1-LIKE 1 and LYSINE-SPECIFIC DEMETHYLASE 1-LIKE 2 (LDL1 and LDL2). Genome-wide DNA methylation analyses reveal that both families cooperate to maintain RdDM patterns. ChIP-seq experiments show that regions that exhibit an observable DNA methylation decrease are co-incidental with increases in H3K4m2/m3. Interestingly, the impact on DNA methylation was stronger at DNA-methylated regions adjacent to H3K4m2/m3-marked protein-coding genes, suggesting that the activity of H3K4 demethylases may be particularly crucial to prevent spreading of active epigenetic marks. Finally, RNA sequencing analyses indicate that at RdDM targets, the increase of H3K4m2/m3 is not generally associated with transcriptional de-repression. This suggests that the histone mark itself—not transcription—impacts the extent of RdDM. A number of factors contribute to the organization of eukaryotic genomes and the expression state of the underlying genes. For example, cytosine bases can be modified with the addition of a methyl-group. In the model plant Arabidopsis thaliana, methylated cytosines are typically associated with transcriptionally repressed regions—so called “heterochromatin.” Additionally, genomic DNA is wrapped around nucleosomes; each nucleosome consists of a complex of eight histone proteins. In turn, amino acid residues on histone proteins can be modified by a number of means, one of which is methylation. A methyl modification on lysine four of histone three (H3K4) is associated with transcriptional activation. Genome-wide studies in Arabidopsis have previously shown that DNA methylation and H3K4 methylation are highly anti-correlated. In this paper we examine a set of Arabidopsis mutants in which H3K4 methylation is abnormally high at a number of loci in the genome. At several of these loci, DNA methylation levels are decreased in the same mutants. These data suggest that H3K4 methylation antagonizes DNA methylation, which may contribute to mechanisms that distinguish active from silent regions of the genome.
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影响因子：
64.8
作者：
Lee, MG;Wynder, C;Shiekhattar, R
通讯作者：
Shiekhattar, R
DOI：
10.1007/978-1-61779-089-8_16
发表时间：
2011-01-01
期刊：
HIGH-THROUGHPUT NEXT GENERATION SEQUENCING: METHODS AND APPLICATION
影响因子：
--
作者：
Feng, Suhua;Rubbi, Liudmilla;Pellegrini, Matteo
通讯作者：
Pellegrini, Matteo
将RNA定向DNA甲基化的两步募集到串联重复序列。
影响因子：
9.8
作者：
Chan, Simon W-L;Zhang, Xiaoyu;Bernatavichute, Yana V;Jacobsen, Steven E
通讯作者：
Jacobsen, Steven E
影响因子：
7.2
作者：
Clough, SJ;Bent, AF
通讯作者：
Bent, AF
DOI：
10.1038/nrg2719
发表时间：
2010-03
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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