One protein’s role in genomic intermingling and T cell development

The findings, from a team led by Golnaz Vahedi of Penn Medicine, could have implications for T-cell based immunotherapies for cancer and other conditions.

Mammalian DNA is folded in 3D structures that create different “neighborhoods” in the genome. These sections of DNA, formally called “topologically associating domains,” remain insulated from each other in order to control how genes get expressed. But when a piece of DNA in one neighborhood is required to control and develop a unique set of genes in another, the neighborhoods must then intermingle.

image of two fuzzy green rings touching represent two T cells

According to a study led by Golnaz Vahedi at the Perelman School of Medicine, one protein, called TCF-1, allows various parts of these otherwise insulated DNA to mix in way that’s required for the T cells—a key element of the body’s immune system—to develop. The role this protein plays in T cell creation could shed new light on immunotherapy approaches. The team published its findings in Nature Immunology.

By studying the mechanics of the protein TCF-1 and how it reconfigures the genome, Vahedi, an associate professor of genetics and a member of the Penn Institute for Immunology and Penn Epigenetics Institute, and colleagues, discovered that the TCF-1 protein has a unique ability to enable plasticity in cells across neighborhoods during the development of T cells.

“These domains, or insulated neighborhoods, are like stickers for social distancing,” Vahedi says. “They essentially say, ‘Stay away—keep a certain distance apart.’ But what this protein does is to remove these stickers and say, ‘You can now actually intermingle.’ It disrupts the spatial distancing.”

Read more at Penn Medicine News.