Researchers have produced the most detailed map to date of how DNA is organized and operates inside living cells. This new view reveals the physical structures that control when and how genes are activated.
The study, published in Cell, was carried out by a team including scientists from the University of Cambridge. They used a method called MCC ultra to map the human genome at single base pair resolution. This approach helps explain how genetic instructions are managed within cells.
“For the first time, we can see how the genome’s control switches are physically arranged inside cells,” said Professor James Davies from the University of Oxford, who led the research. “This changes our understanding of how genes work and how things go wrong in disease. We can now see how changes in the intricate structure of DNA leads to conditions like heart disease, autoimmune disorders and cancer.”
Although scientists have known the full sequence of human DNA for over 20 years, details about its folding and function inside cells remained unclear. DNA is packed tightly into a very small space in each cell, forming loops and bends that bring distant regions together. These three-dimensional shapes influence which genes are turned on or off.
Previously, researchers could only observe these interactions at low resolution. The MCC ultra technique allows them to see these details down to individual base pairs—the smallest building blocks of DNA.
This advance is significant because most genetic variations linked to common diseases occur not within genes themselves but in regulatory regions that act as switches for gene activity. Being able to visualize these regions helps identify where gene regulation fails and could point toward ways to fix it.
The research team collaborated with Professor Rosana Collepardo-Guevara from Cambridge’s Department of Genetics and Yusuf Hamied Department of Chemistry. Her group ran computer simulations confirming that the observed DNA folding patterns result naturally from physical properties of DNA and its associated proteins.
“The MCC ultra technique gives us the most detailed view yet of DNA organisation inside living cells – an order of magnitude higher than the current state of the art,” said Collepardo-Guevara. “Our simulation work also showed that it’s possible to predict the complex 3D structure of the genome in a computer model, which could help us understand in fine detail what goes wrong in disease, and how to fix it.”
The researchers propose a new model for gene regulation: cells use electromagnetic forces to move regulatory sequences toward cell surfaces, where they cluster into islands responsible for gene activity. These previously unseen structures may be central to how cells interpret genetic instructions.
Funding for this work came from several organizations including the Medical Research Council, Lister Institute, Wellcome Trust, and NIHR Oxford Biomedical Research Centre. Simulations at Cambridge were performed by Dr Jan Huertas and Dr Julia Maristany under Collepardo-Guevara’s supervision.
Reference:
Hangpeng Li et al. ‘Mapping chromatin structure at base-pair resolution unveils a unified model of cis-regulatory element interactions.’ Cell (2025). DOI: 10.1016/j.cell.2025.10.013