Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, California, USA.
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Nat Struct Mol Biol. 2014 Jan;21(1):64-72. doi: 10.1038/nsmb.2735. Epub 2013 Dec 15.
DNA methylation occurs in CG and non-CG sequence contexts. Non-CG methylation is abundant in plants and is mediated by CHROMOMETHYLASE (CMT) and DOMAINS REARRANGED METHYLTRANSFERASE (DRM) proteins; however, its roles remain poorly understood. Here we characterize the roles of non-CG methylation in Arabidopsis thaliana. We show that a poorly characterized methyltransferase, CMT2, is a functional methyltransferase in vitro and in vivo. CMT2 preferentially binds histone H3 Lys9 (H3K9) dimethylation and methylates non-CG cytosines that are regulated by H3K9 methylation. We revealed the contributions and redundancies between each non-CG methyltransferase in DNA methylation patterning and in regulating transcription. We also demonstrate extensive dependencies of small-RNA accumulation and H3K9 methylation patterning on non-CG methylation, suggesting self-reinforcing mechanisms between these epigenetic factors. The results suggest that non-CG methylation patterns are critical in shaping the landscapes of histone modification and small noncoding RNA.
DNA 甲基化发生在 CG 和非 CG 序列环境中。非 CG 甲基化在植物中很丰富，由 CHROMOMETHYLASE（CMT）和 DOMAINS REARRANGED METHYLTRANSFERASE（DRM）蛋白介导；然而，其作用仍知之甚少。在这里，我们描述了非 CG 甲基化在拟南芥中的作用。我们表明，一种特征不明显的甲基转移酶 CMT2 在体外和体内都是一种功能性的甲基转移酶。CMT2 优先结合组蛋白 H3 赖氨酸 9（H3K9）二甲基化，并甲基化受 H3K9 甲基化调控的非 CG 胞嘧啶。我们揭示了每个非 CG 甲基转移酶在 DNA 甲基化模式和转录调控中的作用和冗余性。我们还证明了小 RNA 积累和 H3K9 甲基化模式与非 CG 甲基化之间的广泛依赖性，这表明这些表观遗传因子之间存在自我强化机制。结果表明，非 CG 甲基化模式对于塑造组蛋白修饰和小非编码 RNA 的景观至关重要。
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