Researchers have uncovered a fundamental rule that governs how genes are physically arranged inside the cell nucleus, and how disruptions to that organization can contribute to human disease. Researchers at the Perelman School of Medicine at the University of Pennsylvania found that a balance between gene activity and the cellular machinery that folds and organizes DNA determines whether genes are pushed to the edge of the nucleus, where they are often silenced.
In the study, published today in Molecular Cell, the multidisciplinary team shows that this mechanism is disrupted in Friedreich's ataxia (FRDA), a rare inherited neurodegenerative and cardiac disorder, and that re-tuning this balance can partially restore activity of the disease-causing gene.
"This work shows that it's not an either‑or situation," said Rajan Jain, MD, the William Wikoff Smith Associate Professor of Cardiovascular Research, and senior author of the study. "Gene activity and the machinery that folds DNA work together like adjustable dials to determine where genes live inside the nucleus and whether they can function properly."
