植物中 CHG DNA 甲基化维持的机制基础。
Mechanistic basis for maintenance of CHG DNA methylation in plants.
机构信息
Department of Biochemistry, University of California, Riverside, CA, 92521, USA.
Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI, 53706, USA.
出版信息
Nat Commun. 2022 Jul 5;13(1):3877. doi: 10.1038/s41467-022-31627-3.
DNA methylation is an evolutionarily conserved epigenetic mechanism essential for transposon silencing and heterochromatin assembly. In plants, DNA methylation widely occurs in the CG, CHG, and CHH (H = A, C, or T) contexts, with the maintenance of CHG methylation mediated by CMT3 chromomethylase. However, how CMT3 interacts with the chromatin environment for faithful maintenance of CHG methylation is unclear. Here we report structure-function characterization of the H3K9me2-directed maintenance of CHG methylation by CMT3 and its Zea mays ortholog ZMET2. Base-specific interactions and DNA deformation coordinately underpin the substrate specificity of CMT3 and ZMET2, while a bivalent readout of H3K9me2 and H3K18 allosterically stimulates substrate binding. Disruption of the interaction with DNA or H3K9me2/H3K18 led to loss of CMT3/ZMET2 activity in vitro and impairment of genome-wide CHG methylation in vivo. Together, our study uncovers how the intricate interplay of CMT3, repressive histone marks, and DNA sequence mediates heterochromatic CHG methylation.
DNA 甲基化是一种进化上保守的表观遗传机制，对于转座子沉默和异染色质组装至关重要。在植物中，DNA 甲基化广泛发生在 CG、CHG 和 CHH（H=A、C 或 T）背景下，CHG 甲基化的维持由 CMT3 染色质甲基转移酶介导。然而，CMT3 如何与染色质环境相互作用以实现 CHG 甲基化的忠实维持尚不清楚。在这里，我们报告了 CMT3 及其玉米同源物 ZMET2 对 H3K9me2 指导的 CHG 甲基化维持的结构-功能特征。碱基特异性相互作用和 DNA 变形共同为 CMT3 和 ZMET2 的底物特异性提供了基础，而 H3K9me2 和 H3K18 的双价读数则变构地刺激了底物结合。与 DNA 或 H3K9me2/H3K18 的相互作用的破坏导致 CMT3/ZMET2 在体外的活性丧失，以及体内全基因组 CHG 甲基化的损伤。总之，我们的研究揭示了 CMT3、抑制性组蛋白标记和 DNA 序列如何相互作用来介导异染色质 CHG 甲基化。
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