An Unprecedented View of Gene Regulation

MIT engineers have created a new technique that analyzes the 3D organization of the genome at a resolution 100 times higher than before. The findings suggest that many genes interact with dozens of different regulatory elements, although further study is needed to determine which of those interactions are the most important to the regulation of a given gene. Watch this video to learn more about this never-before-seen view.

“Using this method, we generate the highest-resolution maps of the 3D genome that have ever been generated, and what we see are a lot of interactions between enhancers and promoters that haven't been seen previously,” says Anders Sejr Hansen  , the Underwood-Prescott Career Development Assistant Professor of Biological Engineering at MIT and the senior author of the study.

Transcript

00:00:00 [MUSIC PLAYING] VIRAAT GOEL: All of the DNA that makes you you exists inside each and every one of the trillions of cells in your body. And we call this the genome. The genome consists of tiny little DNA segments, some of which contain instructions for doing different things and making you into the person that you are. And we call these small segments genes.

00:00:22 We know that our genes are primarily regulated by other DNA segments called enhancers, which can be located close to or very far away from the genes that they regulate. Over the last 20 years, researchers have struggled to resolve and really see these enhancer gene interactions. And the astronomically high costs of these research studies has prevented us from beginning to understand the mechanisms that govern gene activation.

00:00:49 To solve this problem, we've engineered a new method, which we call Region Capture Micro-C, which allows us to resolve these DNA-DNA genomic interactions at unprecedented resolution and at a fraction of the cost of other methods. Our technique works by chopping up the genome into lots of tiny little pieces, which we can then link back together close to their 3D space neighbors and then read out using sequencing to understand which pieces of the genome are interacting with which

00:01:18 others and ultimately construct an interaction map for the genome. The visual differences between the data we can see from our method and the data we see from other methods is visually striking. Each dark point on this map represents a contact between an enhancer and a gene. And as we zoom in closer and closer and closer to the genome, we continue to be able to resolve these very fine scale interactions

00:01:44 between individual genes and individual enhancers. Being able to resolve these interactions for the first time ultimately allows us to begin to extract the mechanisms that control gene activation.