DNA Methylation States Mix and Mingle on the Nuclear Dance Floor

August 31, 2010 Remember those lame junior high dances, where most of us stood silently and uncomfortably against the gym wall, watching our wilder classmates rock out to Bon Jovi on the dance floor? Some researchers think that methylated and unmethylated promoters in tumors segregate themselves in the same way: silenced genes gather in heterochromatin at the nuclear periphery, while unmethylated genes get active in euchromatin at the center. But recent work by Stephen Baylin at Johns Hopkins and colleagues suggests that there’s more mingling going on in the nucleus than originally thought.

The team used immunostaining and FISH to localize active and repressive chromatin marks within the nuclei of colorectal cancer cell lines. Then, they analyzed the spatial positions of four genes that are often hypermethylated in colorectal cancer cells. Their results were surprising: 


• Hypermethylation-induced silencing took place in both euchromatic and heterochromatic environments.
• Not only that, long-range epigenetic silencing, in which silencing spreads from a hypermethylated promoter to neighboring genes, occurred independently of nuclear location.

These findings in cancer cells contrast with work in development and differentiation systems in which silenced genes were shown to reposition from euchromatin to heterochromatin. The researchers note that future studies comparing matched tumor and normal colon cells will be important to understand the importance of the nuclear reorganization that accompanies tumorigenesis.

Check it out at Cancer Research August 24, 2010.