How DNA folding controls immune gene activity in T cells
University of Pennsylvania School of Medicine
A new study from researchers in the Perelman School of Medicine the University of Pennsylvania reveals that the three-dimensional folding of DNA at a key genetic locus helps determine when two related immune genes, Ets1 and Fli1, are switched on in T cells. Using advanced imaging and mice lacking a critical DNA control region called a super-enhancer, researchers showed that this folding pattern changes as T cells mature into specialized “Th1” cells that help fight certain infections and inflammation. When the super-enhancer is removed, the DNA structure becomes disordered and gene activity is disrupted.
The findings offer new insight into why small genetic variations near these genes may increase risk for immune disorders. “Our work shows that the physical positioning of regulatory DNA elements is not just structural, it actively shapes how T cells decide their identity,” said Golnaz Vahedi, PhD, a professor of Genetics at Penn Medicine and co-author of the study. “Understanding these spatial rules could ultimately help us target the root causes of T cell–mediated diseases more precisely.”
Read the full study in Immunity.
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