Mechanistic basis for maintenance of CHG DNA methylation in plants

Jian Fang, Jianjun Jiang, Sarah M. Leichter, Jie Liu, Mahamaya Biswal, Nelli Khudaverdyan, Xuehua Zhong, Jikui Song

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Article number3877
JournalNature communications
Issue number1
StatePublished - Dec 2022


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