DNA methylation is a major epigenetic modification and plays a crucial role in 
the regulation of gene expression. Within the family of DNA methyltransferases 
(Dnmts), Dnmt3a and 3b establish methylation marks during early development, 
while Dnmt1 maintains methylation patterns after DNA replication. The 
maintenance function of Dnmt1 is regulated by its large regulatory N-terminal 
domain that interacts with other chromatin factors and is essential for the 
recognition of hemi-methylated DNA. Gelfiltration analysis showed that purified 
Dnmt1 elutes at an apparent molecular weight corresponding to the size of a 
dimer. With protein interaction assays we could show that Dnmt1 interacts with 
itself through its N-terminal regulatory domain. By deletion analysis and 
co-immunoprecipitations we mapped the dimerization domain to the targeting 
sequence TS that is located in the center of the N-terminal domain (amino acids 
310-629) and was previously shown to mediate replication independent association 
with heterochromatin at chromocenters. Further mutational analyses suggested 
that the dimeric complex has a bipartite interaction interface and is formed in 
a head-to-head orientation. Dnmt1 dimer formation could facilitate the 
discrimination of hemi-methylated target sites as has been found for other 
palindromic DNA sequence recognizing enzymes. These results assign an additional 
function to the TS domain and raise the interesting question how these functions 
are spatially and temporarily co-ordinated.