Inheritance of epigenetic information encoded by cytosine DNA methylation 
patterns is crucial for mammalian cell survival, in large part through the 
activity of the maintenance DNA methyltransferase (DNMT1). Here, we show that 
SET7, a known histone methyltransferase, is involved in the regulation of 
protein stability of DNMT1. SET7 colocalizes and directly interacts with DNMT1 
and specifically monomethylates Lys-142 of DNMT1. Methylated DNMT1 peaks during 
the S and G(2) phases of the cell cycle and is prone to proteasome-mediated 
degradation. Overexpression of SET7 leads to decreased DNMT1 levels, and 
siRNA-mediated knockdown of SET7 stabilizes DNMT1. These results demonstrate 
that signaling through SET7 represents a means of DNMT1 enzyme turnover.