Role of the arabidopsis DRM methyltransferases in de novo DNA methylation and gene silencing.
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.
Cao
Xiaofeng
X
Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles 90095, USA.
Jacobsen
Steven E
SE
D000595:Amino Acid Sequence; D017360:Arabidopsis / Q000201:enzymology / Q000235:genetics; D029681:Arabidopsis Proteins; D019175:DNA Methylation; D015257:DNA-Cytosine Methylases / Q000235:genetics / Q000502:physiology*; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics*; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010940:Plant Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*; D019076:Transgenes
D029681:Arabidopsis Proteins; C416366:FWA protein, Arabidopsis; D018398:Homeodomain Proteins; D010940:Plant Proteins; D014157:Transcription Factors; C096661:superman protein, Arabidopsis; D015257:DNA-Cytosine Methylases; D008780:Methyltransferases; C470731:DRM1 protein, Arabidopsis; C470732:DRM2 protein, Arabidopsis