Each human cell packs about two metres of DNA into a nucleus one-hundredth of a millimetre across, and the way that DNA bends and loops determines which genes are active, much as a circuit board determines which switches connect. Scientists have known the genome's three billion letters for two decades, but its physical organisation has been visible only at coarse resolution. Researchers at Oxford's Radcliffe Department of Medicine have now mapped it down to the single base pair, using a technique they call MCC ultra.
The resolution matters because more than 90 per cent of genetic changes linked to common diseases lie not within genes but in the regulatory regions that switch them on and off. Seeing how those switches are physically arranged inside cells gives researchers a framework for working out where regulation goes wrong in conditions such as heart disease, autoimmune disorders and cancer, and where intervention might correct it.
Working with computational collaborators at the University of Cambridge, whose simulations confirmed that the observed folding patterns arise naturally from the physical properties of DNA and its packaging proteins, the team proposes a new model of gene regulation. Beyond its conceptual significance, the method hands drug discovery a molecular-scale map of the genome's control architecture, opening routes to therapies aimed at the switches rather than the genes themselves.