Mechanistic insights into plant SUVH family H3K9 methyltransferases and their binding to context-biased non-CG DNA methylation
Mechanistic insights into plant SUVH family H3K9 methyltransferases and their binding to context-biased non-CG DNA methylation
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DOI：
10.1073/pnas.1809841115
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发表时间：
2018-09-11
影响因子：
11.1
通讯作者：
Du, Jiamu
中科院分区：
文献类型：
--
作者：
Li, Xueqin;Harris, C. Jake;Du, Jiamu
DNA甲基化在基因沉默和维持基因组完整性中发挥作用。在植物中，非CG DNA甲基化通过自我增强环与组蛋白3赖氨酸9二甲基化（H3 K9 me 2）联系在一起。植物特异性变异源3-9同源异型（SUVH）家族H3 K9甲基转移酶（MTases）结合DNA甲基化标记并催化H3 K9甲基化。在这里，我们分析了拟南芥SUVH 6的结构和功能，以了解这类酶如何维持基因组中的甲基化模式。我们发现，SUV H6有一个独特的5-甲基-dC（5 mC）基地翻转机制，涉及拇指环元素。H3底物进入的自抑制受SET结构域环调节，并且在辅因子结合后后SET结构域中的构象转变可以控制催化。体外DNA结合和体内ChIP-seq数据显示，不同的SUVH家族H3 K9 MTase具有不同的DNA结合偏好，将H3 K9甲基化靶向具有不同甲基化DNA序列的位点，解释了植物中的背景偏向性非CG DNA甲基化。
DNA methylation functions in gene silencing and the maintenance of genome integrity. In plants, non-CG DNA methylation is linked through a self-reinforcing loop with histone 3 lysine 9 dimethylation (H3K9me2). The plant-specific SUPPRESSOR OF VARIEGATION 3-9 HOMOLOG (SUVH) family H3K9 methyltransferases (MTases) bind to DNA methylation marks and catalyze H3K9 methylation. Here, we analyzed the structure and function of Arabidopsis thaliana SUVH6 to understand how this class of enzyme maintains methylation patterns in the genome. We reveal that SUVH6 has a distinct 5-methyl-dC (5mC) base-flipping mechanism involving a thumb loop element. Autoinhibition of H3 substrate entry is regulated by a SET domain loop, and a conformational transition in the post-SET domain upon cofactor binding may control catalysis. In vitro DNA binding and in vivo ChIP-seq data reveal that the different SUVH family H3K9 MTases have distinct DNA binding preferences, targeting H3K9 methylation to sites with different methylated DNA sequences, explaining the context biased non-CG DNA methylation in plants.