Mar 18, 2020

Substrate deformation regulates DRM2-mediated DNA methylation in plants

Jian FangJikui Song


DNA methylation is an important epigenetic mechanism that critically regulates gene expression and genomic stability. In plants, Domains Rearranged Methyltransferase 2 (DRM2) preferentially mediates CHH methylation (H=C, T, A), a substrate specificity distinct from that of mammalian DNA methyltransferases. However, the underlying mechanism is unknown. Here, we report structure-function characterizations of DRM2-mediated methylation. An arginine finger from the catalytic loop intercalates into DNA minor groove, inducing large DNA deformation that impacts the substrate specificity of DRM2. To accommodate the substrate deformation, the target recognition domain of DRM2 embraces the enlarged DNA major groove via shape complementarity, disruption of which via C397R mutation shifts the substrate specificity of DRM2 toward CHG DNA. This study uncovers DNA deformation as a mechanism in regulating the substrate specificity of DRM2, implicative of transposon-specific repression in plants.

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Mentioned in this Paper

Subdivision of Intercalated Disc
Genomic Stability
DRM2 protein, Arabidopsis
FTSJD1 gene
Methylcobalamin-coenzyme M methyltransferase
Epigenetic Process

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