The enzymatic control of the setting and maintenance of symmetric and 
non-symmetric DNA methylation patterns in a particular genome context is not 
well understood. Here, we describe a comprehensive analysis of DNA methylation 
patterns generated by high resolution sequencing of hairpin-bisulfite amplicons 
of selected single copy genes and repetitive elements (LINE1, B1, 
IAP-LTR-retrotransposons, and major satellites). The analysis unambiguously 
identifies a substantial amount of regional incomplete methylation maintenance, 
i.e. hemimethylated CpG positions, with variant degrees among cell types. 
Moreover, non-CpG cytosine methylation is confined to ESCs and exclusively 
catalysed by Dnmt3a and Dnmt3b. This sequence position-, cell type-, and 
region-dependent non-CpG methylation is strongly linked to neighboring CpG 
methylation and requires the presence of Dnmt3L. The generation of a 
comprehensive data set of 146,000 CpG dyads was used to apply and develop 
parameter estimated hidden Markov models (HMM) to calculate the relative 
contribution of DNA methyltransferases (Dnmts) for de novo and maintenance DNA 
methylation. The comparative modelling included wild-type ESCs and mutant ESCs 
deficient for Dnmt1, Dnmt3a, Dnmt3b, or Dnmt3a/3b, respectively. The HMM 
analysis identifies a considerable de novo methylation activity for Dnmt1 at 
certain repetitive elements and single copy sequences. Dnmt3a and Dnmt3b 
contribute de novo function. However, both enzymes are also essential to 
maintain symmetrical CpG methylation at distinct repetitive and single copy 
sequences in ESCs.