Download MendeleyStructure of an unfavorable de novo DNA methylation complex of plant methyltransferase ZMET2.
Herle, G., Fang, J., Song, J.(2025) J Mol Biology : 169186-169186
- PubMed: 40335018
- DOI: https://doi.org/10.1016/j.jmb.2025.169186
- Primary Citation of Related Structures:
9MVY - PubMed Abstract:
DNA methylation is an important epigenetic mechanism that controls the assembly of heterochromatin and gene expression. In plants, DNA methylation occurs in both CG and non-CG contexts, with non-CG methylation showing notable substrate sequence dependence. The plant DNA methyltransferase CMT3 mediates maintenance of CHG (H?=?A, C, or T) DNA methylation, with a strong substrate preference for the hemimethylated CWG (W?=?A, T) motif. Yet, the underlying mechanism remains elusive. Here we present a crystal structure of ZMET2, the CMT3 ortholog from Zea mays (maize), in complex with a DNA substrate containing an unmethylated CTG motif and a histone peptide carrying a mimic of the histone H3K9me2 modification. Structural comparison of the ZMET2-CTG complex with the previously reported structure of ZMET2 bound to hemimethylated CAG DNA reveals similar but distinct protein-DNA interactions centered on the CWG motif, providing insight into the methylation state- and substrate sequence-specific ZMET2/CMT3-substrate interaction. Furthermore, our combined structural and biochemical analysis reveals a role for the +3-flanking base of the target cytosine in fine-tuning ZMET2-mediated DNA methylation and its functional interplay with the +1- and +2-flanking sites. Together, these results provide deep mechanistic insights into the substrate specificity of CMT3 DNA methyltransferases in plants.
Organizational Affiliation:
Biophysics Program, University of California, Riverside, CA 92521, USA.
