DNA Loops Drive Tissue Regeneration After Injury

After an injury, cells don’t just switch genes on or off—they also reorganize how DNA is arranged in three-dimensional space inside the nucleus. A new study, published in Science Advances, identifies this reorganization as an essential step in tissue regeneration. The research was led by Montserrat Corominas at the University of Barcelona, in collaboration with researchers in Spain and Switzerland, using an animal model to trace how genome architecture responds to damage. 

Inside the nucleus, DNA associates with proteins to form chromatin, the structure that organizes the genome in eukaryotic cells. During regeneration, certain regions of DNA establish new physical contacts through chromatin loops, which act as bridges linking sequences that sit far apart along the genome’s linear sequence. “This chromatin adopts a complex three-dimensional architecture that allows contacts to be established between regions of the genome that are far apart,” explains Corominas, “and regulates which genes are activated or remain inactive at any given moment.”

The results show that a tissue’s regenerative potential depends not only on which genes are switched on or off after an injury, but also on how DNA is reorganized within the nucleus. That evidence positions the genome’s three-dimensional architecture as a new, previously unrecognized layer of regulation that is essential to regenerative processes, closely tied to the dynamics of chromatin state and structure in the affected tissue.

To investigate this, the researchers used wing imaginal discs from Drosophila melanogaster as a model for regeneration. “Importantly, we have identified three of these DNA loops and have experimentally demonstrated that they are necessary for efficient regeneration,” notes Carlos Camilleri-Robles, one of the study’s lead authors. “When we altered the regions responsible for their formation,” he adds, “the tissues’ regenerative capacity was significantly reduced, while the organism’s normal development remained virtually unaffected.”

“Overall, our results identify a previously unknown role for genome architecture in tissue repair,” says Palmira Llorens-Giralt, the study’s first author, “and reveal an additional layer of regulation of gene expression during regeneration.”