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Scientists from Oxford's Radcliffe Department of Medicine have achieved the most detailed view yet of how DNA folds and functions inside living cells, revealing the physical structures that control when and how genes are switched on.

Using a new technique called MCC ultra, the team mapped the human genome down to a single base pair, unlocking how genes are controlled, or, how the body decides which genes to turn on or off at the right time, in the right cells. This breakthrough gives scientists a powerful new way to understand how genetic differences lead to disease and opens up fresh routes for drug discovery.

"For the first time, we can see how the genome's control switches are physically arranged inside cells, said Professor James Davies, lead author of the published in the journal Cell titled "Mapping chromatin structure at base-pair resolution unveils a unified model of cis-regulatory element interactions."

"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 lead to conditions like heart disease, autoimmune disorders and cancer."

For more than two decades, scientists have known the full sequence of the human genome—the 3 billion "letters" of DNA that make up our genetic code. But exactly how that code folds and functions inside the cell has remained largely hidden.

Each cell's DNA, about 2 meters long, is tightly packed into a microscopic space one-hundredth of a millimeter across. Within this space, the DNA constantly bends and loops, bringing distant sections into contact. These 3D structures are crucial because they determine which genes are active or silent, much like how a circuit board determines which switches are connected and which are not.

Until now, researchers could only view these interactions at relatively low resolution. The new Oxford method captures them down to a single base pair—the smallest unit of DNA—offering a truly molecular view of gene control.

This level of detail matters because more than 90% of genetic changes linked to common diseases lie not within genes themselves, but in the "switch" regions that regulate them. The ability to see how these switches are organized gives scientists a new framework for identifying where gene regulation goes wrong and how it might be corrected.

"We now have a tool that lets us study how genes are controlled in exquisite detail," said Hangpeng Li, the doctoral researcher who led the experimental work. "That's a critical step toward understanding what goes wrong in disease, and what might be done to fix it."

The Oxford team also collaborated with Professor Rosana Collepardo-Guevara at the University of Cambridge, whose computer simulations confirmed that the folding patterns observed arise naturally from the physical properties of DNA and its packaging proteins.

Together, the scientists propose a new model of gene regulation in which cells use electromagnetic forces to bring DNA control sequences to the surface, where they cluster into "islands" of gene activity. These structures, which were previously invisible, appear to be a fundamental mechanism for how cells read their genetic instructions.

The research represents a major advance in molecular genetics, providing a foundation for future studies into how changes in genome structure cause disease.