Video: Altering the human genome in 3D

The 2 meters of DNA squeezed into a human nucleus a few millionths that size is not randomly crammed in. Instead, our cells depend on chromosomes being precisely folded into specific loops that enable the right genes to turn on. Now, researchers have come up with a way to alter those loops by simply changing one “letter” in the DNA defining the loop. Their success is a first step toward a new way to edit genomes, which may not only aid our understanding of how life works, but also may prove useful when genome changes are needed to cure disease. Most immediately, the work lends further support to the idea that loops emerge by being “extruded” through a protein complex (as seen in the video above) that cordons off one section of DNA. Genes and regulatory DNA in that section can then interact, even though they are normally far apart on the chromosome. Other recent work on looping bolstered the case for extrusion as well. For this new study, the researchers first identified many instances of DNA sequences involved in looping. Then they developed a mathematical model that predicted where looping should occur and what letter or base change would change a particular loop. In all 13 of 13 tries, that change did what they predicted, they reported this week in the Proceedings of the National Academy of Sciences. The work will make it easier for everyone to predict the genome’s 3D configuration based simply on knowing where certain DNA sequences are, the researchers note.