727 E. Tyler St. Tempe
To a physicist, epigenetics – the passing of heritable traits to daughter cells without alteration of the genome – seems like magic. Yet it surely lies at the heart of cancer, as cancerous phenotypes can be switched on and off without alteration of the genome. Together with the Henikoff lab at Fred Hutchinson Cancer Research Center, we have been looking for physical manifestations of epigenetic coding. We started by looking at modifications and variants of histones, but these seem to be unlikely candidates for heritable markers. Instead, it appears that transcription factors (which are passed on at cell division) are the controlling factor. We have also studied methylation of DNA, a modification that imparts permanent silencing. Nucleosomes reconstituted on methylated DNA are intrinsically harder to open, implying a mechanical change in the DNA on methylation. Light scattering studies(by Sara Vaiana and Stephanie Cope) shows that methylation makes no difference in bulk solution. In contrast, AFM studies show that DNA shortens and stiffens with methylation at a solid-liquid interface. We therefore conclude that the hydrophobic interaction plays a role in keeping methylated DNA in place on nucleosomes.