Proper DNA methylation patterning requires the complementary processes of de 
novo methylation (the initial methylation of unmethylated DNA sequences) and 
maintenance methylation (the faithful replication of preexisting methylation). 
Arabidopsis has two types of methyltransferases with demonstrated maintenance 
activity: MET1, which maintains CpG methylation and is homologous to mammalian 
DNMT1, and CHROMOMETHYLASE 3 (CMT3), which maintains CpNpG (N = A, T, C, or G) 
methylation and is unique to the plant kingdom. Here we describe 
loss-of-function mutations in the Arabidopsis DOMAINS REARRANGED METHYLASE (DRM) 
genes and provide evidence that they encode de novo methyltransferases. drm1 
drm2 double mutants retained preexisting CpG methylation at the endogenous FWA 
locus but blocked de novo CpG methylation that is normally associated with FWA 
transgene silencing. Furthermore, drm1 drm2 double mutants blocked de novo CpNpG 
and asymmetric methylation and gene silencing of the endogenous SUPERMAN (SUP) 
gene, which is normally triggered by an inverted SUP repeat. However, drm1 drm2 
double mutants did not show reactivation of previously established SUPERMAN 
epigenetic silenced alleles. Thus, drm mutants prevent the establishment but not 
the maintenance of gene silencing at FWA and SUP, suggesting that the DRMs 
encode the major de novo methylation enzymes affecting these genes.