Fig. 7.

Schematic diagram of regulation of the 14-3-3σ gene by reversible methylation during gemcitabine selection. In MiaPaCa-2 cells, a high level of Uhrf1 binds to and helps recruit DNMT1 to the methylated region of the 14-3-3σ gene to maintain methylation. In G3K cells, Uhrf1 expression is reduced and serves as a limiting factor. Thus, little DNMT1 is recruited to the 14-3-3σ gene to maintain methylation despite the presence of a high level of DNMT1. In G3K/REV cells, the increase in Uhrf1 level helps recruit more DNMT1 protein to the 14-3-3σ gene, resulting in more methylation and partial loss of 14-3-3σ expression.