Interview with Dr. Jennifer Phillips-Cremins at Keystone Symposia’s Precision Genome Engineering and Synthetic Biology.
My lab is really focused on understanding the epigenetic mechanisms that regulate early brain development. And the, sort of traditional way of studying epigenetic marks, is to zoom in and really focus on a particular modification at a precise location in the genome. In our case, we take a different approach.
We take a top down approach in which we first map the higher order folding of chromatin, and then we look to see how different epigenetic modifications work through long range regulatory mechanisms to ultimately govern gene expression. So this is a bit different, in that you might assume that epigenetic marks separated by vast differences on chromatin might have absolutely nothing to do with each other when it comes to regulating gene expression. But it turns out, if you consider the genome in its three dimensional state, that these marks might be actually adjacent to each other and regulate each other very interesting ways.
And for my lab in particular, we’re very interested in the brain and how lineage commitment comes about as cells mature in the brain and central nervous system.
Oh, I think where we are as a field is, we really have a nice grasp, when you think of the linear chromatin and the chromatin signatures. Histone modification combinations that mark different types of genes, poise genes, elongated jeans, initiated genes, inactive genes. Or even enhancers. We have poison enhancers, active enhancers, and perhaps this new class of potentially super enhancers.
So we have a good handle on that. What are the chromatin signatures that perhaps predict that those particular genomic loci will serve that particular function in a cell, in that cellular state?
Taking Chromatin Analysis 3D
The area where my lab is most interested right now, actually, is trying to translate that to 3D. And how it is the three dimensional structure of the chromatin either aid in laying down those marks and establishing the particular signatures that ultimately regulate gene expression, or, in reverse manner, perhaps the chromatin marks then in turn manipulate chromatin architecture in some way, before or after gene expression is established or maintained.
So these are all very interesting things that, in my opinion, where the field is, is we don’t quite understand it altogether. The main pioneer in this area has really been Gerd Blobel, who has done some work in the beta globin locus, using genome editing techniques to try to understand the link between looping and initiation and elongation. And he’s made some nice steps there. But there’s a lot more to go.