By Stem Cell Blogger | April 16, 2010 at 05:04 PM EDT | No Comments
What if we really could take a snapshot of a cell's epigenome? I think it would tell us an enormous amount of the identity of the cell and what makes it tick. However, the epigenome is many orders of magnitude more complex than the genome. Also, while the genome is fairly static, the epigenome is inherently dynamic, constantly visited by trillions of molecules of likely 100s of types of enzymes that tinker with it.
So if one is look for a cancer-causing mutation in the genome, it may be a challenge to find it but it is doable. But if one is looking cancer-causing epi-mutations, it is much more difficult. There are likely suspects already including specific modifications of lysine residues in histones and certain spots of DNA methylation, but the complexity of the epigenome means that not only every cancer type, but every cancer cell has its own epigenomic signature consisting of a mindboggling combination of different possible histone modifications and DNA methylation events. No, it can't be that complex you say? Well, how many possible combinations of histone and DNA modifications are possible within an octamer of a single nucleosome? It's got to be hundreds or thousands.
So what to do? The current approach of looking for defining events that fairly consistently show up in say cancer cells versus normal cells is working, but is too slow. We need new more powerful technology to "sequence" the epigenome....I don't know what that technology will be but current methods such as ChIP-Seq, while really revolutionary, still cannot handle the complexity of the epigenome.