Researchers have been able to model the structure of chromosomes when they are active using a novel approach.

This is important because the way in which DNA folds up into chromosome structures is intimately linked to the way DNA is used, controlling when and how strongly genes are expressed. It is also critical in the development of organisms and in disease.

Chromosome structure is commonly illustrated as an X shape, present only when the cell divides, but researchers from the University of Cambridge, the Babraham Institute and the Weizmann Institute can now see the structure of chromosomes when they are active.

They used hundreds of measurements of where different parts of DNA get close to one another, with their new approach showing them the complex way in which DNA folds up into working chromosomes and where the genes lie in three dimensions.

This means they can study how specific genes and the DNA regions that control them, interact with each other to better understand how chromosomes work.

“It took several years to develop all the computational tools to make this happen, but the structures we can now reconstruct from this high-quality data are quite striking,” said Tim Stevens, who wrote the software to calculate and visualise the structures. “More importantly, this new approach is allowing us to study the variation in chromosome structure on a cell-by-cell basis.”

Knowing where all the genes and the elements that control them at any given moment will help scientists to understand the molecular mechanisms that control and maintain the genome, said Stevens. In the future the group will be looking at individual decisions made by single developing stem cells in that population, at least from the outside, appear to be uniform.

“These mechanisms are currently poorly understood and understanding them may be key to realising the potential of stem cells in medicine,” Stevens said.