How is DNA methylation targeted in normal cells & what goes wrong in cancer?  In normal cells (top) DNA methylation is concentrated in repetitive regions of the genome and most CpG island promoters are unmethylated.  In tumor cells, the compartmentalization breaks down and repetitive DNA loses methylation while CpG island promoters acquire it, resulting in silencing of the associated gene.  The DNMTs are likely targeted to particular regions via protein-protein interactions within chromatin and understanding this process is a major focus of the lab.