Department of Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America.
PLoS Genet. 2013 Nov;9(11):e1003946. doi: 10.1371/journal.pgen.1003946. Epub 2013 Nov 7.
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.
DNA 甲基化是一种表观遗传标记，与转座元件和蛋白质编码基因的转录抑制有关。相反，转录活跃的调控区域与组蛋白 3 赖氨酸 4 二甲基化和三甲基化（H3K4m2/m3）强烈相关。我们之前表明，拟南芥植物中 H3K4m2/m3 去甲基酶 JUMONJI 14（JMJ14）的突变会导致 RNA 指导的 DNA 甲基化（RdDM）轻微减少，这与 H3K4m2/m3 水平升高有关。为了确定这种不完全的 RdDM 减少是否是由于与其他去甲基酶的冗余，我们研究了 JMJ14 与另一类 H3K4 去甲基酶的遗传相互作用：赖氨酸特异性去甲基酶 1 样 1 和赖氨酸特异性去甲基酶 1 样 2（LDL1 和 LDL2）。全基因组 DNA 甲基化分析表明，这两个家族合作以维持 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 H3K4m2/m3 的增加相一致。有趣的是，这种对 DNA 甲基化的影响在靠近 H3K4m2/m3 标记的蛋白质编码基因的 DNA 甲基化区域更为强烈，这表明 H3K4 去甲基酶的活性可能对防止活性表观遗传标记的扩散特别重要。最后，RNA 测序分析表明，在 RdDM 靶标中，H3K4m2/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。
