In mammals Dnmt1 is the DNA methyltransferase chiefly responsible for 
maintaining genomic methylation patterns through DNA replication cycles, but how 
its maintenance activity is controlled is still not well understood. 
Interestingly, Uhrf1, a crucial cofactor for maintenance of DNA methylation by 
Dnmt1, is endowed with E3 ubiquitin ligase activity. Here, we show that both 
Dnmt1 and Uhrf1 coprecipitate with ubiquitin specific peptidase 7 (Usp7), a 
de-ubiquitinating enzyme. Overexpression of Uhrf1 and Usp7 resulted in opposite 
changes in the ubiquitination status and stability of Dnmt1. Our findings 
suggest that, by balancing Dnmt1 ubiquitination, Usp7 and Uhrf1 fine tune Dnmt1 
stability.