Substrate deformation regulates DRM2-mediated DNA methylation in plants

Jian Fang, Sarah M. Leichter, Jianjun Jiang, Mahamaya Biswal, Jiuwei Lu, Zhi Min Zhang, Wendan Ren, Jixian Zhai, Qiang Cui, Xuehua Zhong, Jikui Song

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


DNA methylation is a major epigenetic mechanism critical for gene expression and genome stability. In plants, domains rearranged methyltransferase 2 (DRM2) preferentially mediates CHH (H = C, T, or A) methylation, a substrate specificity distinct from that of mammalian DNA methyltransferases. However, the underlying mechanism is unknown. Here, we report structure-function characterization of DRM2-mediated methylation. An arginine finger from the catalytic loop intercalates into the nontarget strand of DNA through the minor groove, inducing large DNA deformation that affects the substrate preference of DRM2. The target recognition domain stabilizes the enlarged major groove via shape complementarity rather than base-specific interactions, permitting substrate diversity. The engineered DRM2 C397R mutation introduces base-specific contacts with the +2-flanking guanine, thereby shifting the substrate specificity of DRM2 toward CHG DNA. Together, this study uncovers DNA deformation as a mechanism in regulating the specificity of DRM2 toward diverse CHH substrates and illustrates methylome complexity in plants.

Original languageEnglish
Article numbereabd9224
JournalScience Advances
Issue number23
StatePublished - Jun 2021


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