Arabidopsis EDM2 promotes IBM1 distal polyadenylation and regulates genome DNA methylation patterns
Arabidopsis EDM2 promotes IBM1 distal polyadenylation and regulates genome DNA methylation patterns
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拟南芥 EDM2 促进 IBM1 远端聚腺苷酸化并调节基因组 DNA 甲基化模式
DOI：
10.1073/pnas.1320106110
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发表时间：
2014-01-07
影响因子：
11.1
通讯作者：
Zhu, Jian-Kang
中科院分区：
文献类型：
--
作者：
Lei, Mingguang;La, Honggui;Zhu, Jian-Kang
组蛋白3赖氨酸9去甲基化酶在盆栽甲基化1 （IBM1）中的增加是防止植物基因中CHG （H=A， T，或C）甲基化的关键。研究人员发现，被认为是染色质调节剂的增强型霜霉2 （Enhanced Downy Mildew 2, EDM2）通过调节IBM1的选择性聚腺苷化来控制基因组CHG甲基化和转基因沉默。EDM2包含一个复合的植物同源结构域，可以同时识别抑制性和活性组蛋白标记，使其与IBM1和其他植物基因的内含子异染色质特异性结合，从而通过n6 -腺嘌呤甲基转移酶样活性使RNA甲基化，从而影响多腺苷化。这项工作极大地促进了我们对含内含子异染色质基因的DNA甲基组调控和抗沉默和选择性聚腺苷化机制的理解。在许多高等真核生物中，DNA甲基化对于转座子和其他重复元件的沉默是重要的。然而，植物和哺乳动物的基因组已经进化到在它们的基因附近或内部包含重复的元素。这些基因是如何不被DNA甲基化沉默的，目前还不清楚。一项正向遗传学筛选鉴定了染色质调节剂增强型霜霉病2 （EDM2）作为细胞抗沉默因子和基因组DNA甲基化模式的调节剂。EDM2包含一个复合的植物同源结构域，该结构域可识别组蛋白3赖氨酸9去甲基化基因（IBM1）等基因内含子重复元件上的活性和抑制性组蛋白甲基化标记，并且通过促进mRNA远端聚腺苷化来维持这些基因的表达。由于其在维持IBM1表达中的作用，EDM2是防止体内数千种基因的CHG甲基化所必需的。因此，我们的研究结果增加了对抗沉默、基因组甲基化模式和内含子异染色质对替代RNA加工的调控的理解。
Significance The histone 3 lysine 9 demethylase Increase in BONSAI Methylation 1 (IBM1) is critical for preventing CHG (H=A, T, or C) methylation in plant genes. We found that the putative chromatin regulator Enhanced Downy Mildew 2 (EDM2) controls genome CHG methylation and transgene silencing by regulating alternative polyadenylation of IBM1. EDM2 contains a composite plant homeo domain that simultaneously recognizes both repressive and active histone marks, allowing it to associate specifically with the intronic heterochromatin of IBM1 and other plant genes so that it may affect polyadenylation by methylating the RNA through an N6-adenine methyltransferase-like activity. This work significantly advances our understanding of the regulation of DNA methylome and mechanisms of antisilencing and alternative polyadenylation of intronic heterochromatin-containing genes. DNA methylation is important for the silencing of transposons and other repetitive elements in many higher eukaryotes. However, plant and mammalian genomes have evolved to contain repetitive elements near or inside their genes. How these genes are kept from being silenced by DNA methylation is not well understood. A forward genetics screen led to the identification of the putative chromatin regulator Enhanced Downy Mildew 2 (EDM2) as a cellular antisilencing factor and regulator of genome DNA methylation patterns. EDM2 contains a composite Plant Homeo Domain that recognizes both active and repressive histone methylation marks at the intronic repeat elements in genes such as the Histone 3 lysine 9 demethylase gene Increase in BONSAI Methylation 1 (IBM1) and is necessary for maintaining the expression of these genes by promoting mRNA distal polyadenylation. Because of its role in maintaining IBM1 expression, EDM2 is required for preventing CHG methylation in the bodies of thousands of genes. Our results thus increase the understanding of antisilencing, genome methylation patterns, and regulation of alternative RNA processing by intronic heterochromatin.