It’s no fun to get put in the “hot seat”. Whether it’s your advisor ragging on you for not having enough data; or your sweetie reminding you that you forgot your anniversary. Again. In either case, you sink lower and lower into your chair, and your muscles tighten while you take what you have coming. Researchers at Stanford (including Steven Chu, AKA the current U.S. Energy Secretary) and Penn State say that the same thing happens when methyl groups are hooked onto DNA, creating nucleosomes that get smaller and less flexible.
Sure, methylated CpGs can repress transcription by binding to repressors or blocking activators from binding to DNA. But methylation also could change nucleosomal structure—which is what these researchers wanted to test. Some tricky chemistry techniques, such as fluorescence resonance energy transfer (FRET) and fluorescence anisotropy, told them the answer.
The fun began when nucleosomes were treated with M.SssI CpG methyltransferase in order to compare methylated to non-methylated CpGs. Here’s what they saw:
- With FRET, they saw a 40-fold increase in complexes with lots of DNA—histone contacts (a “high-FRET” state), suggesting a more compact nucleosome structure.
- Highly polarized emissions from high-FRET state complexes indicated that methylated DNA becomes more rigid.
Get all wrapped up in the full story at the Journal of the American Chemical Society, January 2010.