How DNA folding controls immune gene activity in T cells

Researchers at the Perelman School of Medicine at the University of Pennsylvania have uncovered the role of DNA folding in controlling the activity of immune genes in T cells. The study, published in the journal Immunity, demonstrates that the three-dimensional folding of DNA at the Ets1–Fli1 locus influences when these immune genes switch on during T-cell differentiation into Th1 cells.

Using advanced imaging techniques and mice lacking a crucial DNA control region called a super-enhancer, the researchers found that the folding pattern of the DNA changes as T cells mature into specialized Th1 cells. When the super-enhancer is absent, the DNA structure becomes disordered, leading to disrupted gene activity.

This finding provides insight into how small genetic variations near these immune genes might increase the risk of immune disorders. Dr. Golnaz Vahedi, a professor of genetics at Penn Medicine and co-author of the study, notes that "the physical positioning of regulatory DNA elements is not just structural; it actively shapes how T cells decide their identity."

Understanding these spatial rules could enable more precise targeting of the root causes of T cell–mediated diseases. This study, titled "Single-allele chromatin tracing reveals cytokine-dependent super-enhancer repositioning in CD4+ T cells," was conducted by Atishay Jay et al.