Site-specific methylation of cytosines is a key epigenetic mark of vertebrate 
DNA. While a majority of the methylated residues are in the symmetrical 
(meC)pG:Gp(meC) configuration, a smaller, but significant fraction is found in 
the CpA, CpT and CpC asymmetric (non-CpG) dinucleotides. CpG methylation is 
reproducibly maintained by the activity of the DNA methyltransferase 1 (Dnmt1) 
on the newly replicated hemimethylated substrates (meC)pG:GpC. On the other 
hand, establishment and hereditary maintenance of non-CpG methylation patterns 
have not been analyzed in detail. We previously reported the occurrence of site- 
and allele-specific methylation at both CpG and non-CpG sites. Here we 
characterize a hereditary complex of non-CpG methylation, with the 
transgenerational maintenance of three distinct profiles in a constant ratio, 
associated with extensive CpG methylation. These observations raised the 
question of the signal leading to the maintenance of the pattern of asymmetric 
methylation. The complete non-CpG pattern was reinstated at each generation in 
spite of the fact that the majority of the sperm genomes contained either none 
or only one methylated non-CpG site. This observation led us to the hypothesis 
that the stable CpG patterns might act as blueprints for the maintenance of 
non-CpG DNA methylation. As predicted, non-CpG DNA methylation profiles were 
abrogated in a mutant lacking Dnmt1, the enzymes responsible for CpG 
methylation, but not in mutants defective for either Dnmt3a or Dnmt2.