Researchers at MIT have developed a method that allows them to analyze the three dimensional interactions of sections of the genome in unprecedented detail. The technique could let scientists investigate the origin and progression of genetic diseases, as well as identifying new therapeutic targets for them. The new approach, called Region Capture Micro-C, involves using an enzyme to cut a section of the genome into small and uniform fragments, and then linking pieces of the genome together again that are predicted to interact with each other in the cell nucleus, before finally sequencing the strands to learn their identity. The resulting maps that the researchers create can reveal a host of previously unknown information about how segments of the genome interact with each other to control gene expression.
Genetic expression is complex, involving areas of the genome that can regulate the activity of genes, such as areas called promoters that help to motivate gene expression. While some of these regions lie right next to the gene they affect, others lie far away, requiring the genome to contort in 3D space to bring disparate regions together to enable fine control of gene expression.
To date, it has been too complicated and expensive to unpick all these interactions and fully understand how they work and how they may affect genetic disease. However, appreciating the nuances of genome interactions could shed light on such diseases, and let researchers develop new treatments.
“Researchers can now affordably study the interactions between genes and their regulators, opening a world of possibilities not just for us but also for dozens of labs that have already expressed interest in our method,” said Viraat Goel, a researcher involved in the study. “We’re excited to bring the research community a tool that help them disentangle the mechanisms driving gene regulation.”
The new approach involves focusing on a target area of the genome, instead of the whole thing, helping to drastically reduce costs and time associated with the analysis, but still yielding very detailed data. “Now we have a method for getting ultra-high-resolution 3D genome structure maps in a very affordable manner. Previously, it was so inaccessible financially because you would need millions, if not billions of dollars, to get high resolution,” said Anders Sejr Hansen, another researcher involved in the study. “The one limitation is that you can’t get the whole genome, so you need to know approximately what region you’re interested in, but you can get very high resolution, very affordably.”
Check out an MIT video about the technology:
Study in journal Nature Genetics: Region Capture Micro-C reveals coalescence of enhancers and promoters into nested microcompartments