The drm1 drm2 cmt3 triple mutant plants did not affect CpG methylation at any locus tested, suggesting that the primary CpG methylases are encoded by the MET1 class of genes. Although neither the drm1 drm2 double mutants nor the cmt3 single mutants show morphological defects, drm1 drm2 cmt3 triple mutant plants show pleiotropic effects on plant development. Our results suggest that the DRM and CMT3 genes act in a partially redundant and locus-specific manner to control asymmetric and CpNpG methylation.