7l4m
Crystal structure of the DRM2-CCT DNA complex
Structural highlights
FunctionDRM2_ARATH Involved in de novo DNA methylation. Controls asymmetric and CpNpG methylation. Required for FWA gene silencing but not for the maintenance of SUP gene silencing. Functionally redundant to CMT3 to maintain non-CpG methylation. Involved in RNA-directed DNA methylation (RdDM) (PubMed:12121623, PubMed:12151602, PubMed:14680640). Acts as major DNA methyltransferase in the RdDM pathway, and is essential for RNA-directed de novo DNA methylation of cytosines in all sequence contexts (PubMed:21060858, PubMed:21212233). Associates with long non-coding RNA (lncRNA) produced by RNA polymerase V (Pol V). This association is dependent on AGO4 and IDN2, and results in DNA methylation of RdDM target loci (PubMed:24862207).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedDNA 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. Substrate deformation regulates DRM2-mediated DNA methylation in plants.,Fang J, Leichter SM, Jiang J, Biswal M, Lu J, Zhang ZM, Ren W, Zhai J, Cui Q, Zhong X, Song J Sci Adv. 2021 Jun 2;7(23):eabd9224. doi: 10.1126/sciadv.abd9224. Print 2021 Jun. PMID:34078593[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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