Dr. Wolf Reik discusses the latest advances in epigenetic reprogramming, and what those new discoveries might lead to.
The New DNA Methylation Landscape
So it’s become apparent in the last two years, I guess, that there is this process of genome-wide epigenetic reprogramming which occurs naturally in germ cells, early embryo stem cells, et cetera, and involves this genome-wide erasure of DNA methylation. And that’s really been the focus of quite intense work over the last few years trying to understand– we understand quite well the biology of DNA methylation. But until recently, we haven’t really understood the biology of demethylating DNA.
It’s hugely exciting. Remember the revolution that we saw with the discovery of the histone modifications and the explosion of that field? And in a sense, DNA modification field is experiencing something similar right now. You can see it, how quickly that the work gets out there, the publications are appearing. New people are getting into the field. It’s hugely exciting, actually.
And as you say, it raises the question whether– you can look at it in two ways. You can say, you can have the view that these modifications are intermediate to demethylating DNA. Alternatively, they could also have functions, epigenetic functions, and be epigenetic signals by themselves.
…we understand quite well the biology of DNA methylation. But until recently, we haven’t really understood the biology of demethylating DNA.
And I think the jury is out to say that’s the case. It’s demethylation intermediates. It’s new epigenetic signals. Discovery of proteins that interact with hydroxy, with formyl, with carboxyl is probably just around the corner as well.
Are these going to be proteins that further deal with the modifications and convert them into other things? Or are there proteins out there that act as readers, epigenetic readers, of these modifications as well? And so potentially expand the DNA code in many different dimensions, I think, potentially in the future. I think some of the most exciting developments in the field now is how these factors play together– so how deaminating DNA, oxidizing demethyl-repair pathways, base excision repair, how these different processes are either perhaps parallel processes or interconnected processes. And I think this is one of the most exciting developments in the field.
The Buzz in Reprogramming
I think another really exciting area that’s developing is how can you apply these insights to experimental reprogramming? We know for some time now that in order to generate IPS cells, you need to reprogram, epigenetically reprogram, and in particular reprogram methylation patterns. So if reprogramming methylation patterns is so crucial for generating IPS cells, then how can these factors that are important for demethylation contribute and help to make the derivation of IPS cells better, more faithful, you get better IPS cells. You can apply them better to the study of diseases and perhaps, eventually, in therapy processes as well.