Dr. Jerry Workman shares some of his thoughts on the next steps in digging into biochemistry of epigenetic mechanisms to understand what’s reading and what’s writing.
Epigenetics: Getting to Know the Readers and the Writers
I think the most exciting aspect about epigenetics at this time is the potential it provides for some fantastic biochemistry. Right? And this has kind of been a historical thing, because many, many years ago when we would have what were the equivalents of chromatin in epigenetics meetings. There would be the chromatin people who were doing descriptive biochemistry, and then these genetics people that would come and tell us a bunch of genetic phenomena that they didn’t understand. And they called epigenetics, and we figured since it’s not based on DNA, it must be chromatin.
So for many years, epigenetics must be chromatin, but they didn’t understand. And that stuff really took off when the biochemists started to really tackle and purify the proteins encoded by these genes responsible for epigenetic phenomena. So it’s like the trithorax group and the polycomb group proteins, and the histone acetyltransferase complexes, whatever, and that really kind of broke it down.
Now epigenetics is approachable by the biochemical means, and we can actually see what the proteins, what they do, what the enzymes are, which had not been known before. So that’s become a whole new phase for both the chromatin and the epigenetics field. And even now, with all this talk on various domains or readers, and which different enzymes modify, we really don’t know very much about what those things do. So we have anti-cancer drugs that are histone deacetylase inhibitors, but we don’t really know how that helps prevent cancer.
There’s new drugs coming out that inhibit bromodomains binding to acetylade histones, but we don’t know what bromodomains binding to acetylade histones necessarily means biochemically or mechanistically. And so what the sort of increasing trend that is the epigenetic basis for a lot of diseases, etc., I think that really makes the biochemistry and the mechanistic studies more important. Because if this is really something that we hope to seriously be able to pharmacologically manipulate, we have to know exactly what those enzymes and proteins do. How they work, and what it means before we can really figure out a way to manipulate their activities pharmacologically.