DNA methylation regulates gene expression through a complex network of 
protein-protein and protein-DNA interactions in chromatin. The maintenance 
methylase, DNMT1 (DNA methyltransferase 1), is a prominent enzyme in the process 
that is linked to DNA replication and drives the heritable nature of epigenetic 
modifications. The mechanistic details that explain how DNMT1 catalytic action 
is directed and regulated in chromatin are important in our overall 
understanding of gene control. In this work, we show that DNMT1 is modified by 
SUMOylation and we have mapped these SUMOylation sites by defined mutations. 
SUMOylated DNMT1 is catalytically active on genomic DNA in vivo and we find that 
SUMOylation significantly enhances the methylase activity of DNMT1 both in vitro 
and in chromatin. These data suggest that SUMOylation modulates the endogenous 
activity of a prominent epigenetic maintenance pathway in somatic cells.