CMT3 is essential for maintaining CpXpG methylation in Arabidopsis. Loss-of-function alleles of CMT3 result in decreased CpXpG methylation and reactivation of retrotransposons, indicating that CMT3 is a non-CpG DNA methyltransferase involved in gene silencing. CMT3 encodes a cytosine methyltransferase with a chromodomain and BAH domain. Mutant analysis revealed that CMT3 is required for maintaining CpXpG methylation, which is distinct from the CpG methylation maintained by DNMT1/MET1. CMT3 mutations lead to reduced CpXpG methylation but not CpG methylation, and do not affect CpG methylation or gene silencing at the FWA locus. CMT3 is necessary for maintaining gene silencing at certain retrotransposon sequences. The study shows that CMT3 is specific for CpXpG methylation, and that MET1 cannot substitute for CMT3 at these sites. CMT3 is required for maintaining CpXpG methylation, and its loss leads to reactivation of retrotransposons. Despite a nearly complete loss of genomic CpXpG methylation, null cmt3 mutants are morphologically normal, suggesting that CpXpG and CpG methylation may act redundantly to silence genes. Arabidopsis is an ideal model system for studying DNA methylation in epigenetic and developmental processes.CMT3 is essential for maintaining CpXpG methylation in Arabidopsis. Loss-of-function alleles of CMT3 result in decreased CpXpG methylation and reactivation of retrotransposons, indicating that CMT3 is a non-CpG DNA methyltransferase involved in gene silencing. CMT3 encodes a cytosine methyltransferase with a chromodomain and BAH domain. Mutant analysis revealed that CMT3 is required for maintaining CpXpG methylation, which is distinct from the CpG methylation maintained by DNMT1/MET1. CMT3 mutations lead to reduced CpXpG methylation but not CpG methylation, and do not affect CpG methylation or gene silencing at the FWA locus. CMT3 is necessary for maintaining gene silencing at certain retrotransposon sequences. The study shows that CMT3 is specific for CpXpG methylation, and that MET1 cannot substitute for CMT3 at these sites. CMT3 is required for maintaining CpXpG methylation, and its loss leads to reactivation of retrotransposons. Despite a nearly complete loss of genomic CpXpG methylation, null cmt3 mutants are morphologically normal, suggesting that CpXpG and CpG methylation may act redundantly to silence genes. Arabidopsis is an ideal model system for studying DNA methylation in epigenetic and developmental processes.