AP-1 Transcription Factor a Key Player in T Cell Activation
Published January 2020 | Journal of Experimental Medicine
T cells are vital to helping our bodies fight off illness, cancer, and immune disease. Activating them involves the orchestrated opening and closing of chromatin, the material that packages a cell’s DNA, which makes some gene functions accessible, while making others inaccessible.
Now, a multidisciplinary team of Cincinnati Children’s researchers reports uncovering a vital clue about how this process works. Their study, published in the Journal of Experimental Medicine, reveals that the transcription factor activator protein 1 (AP-1) directs most of the chromatin remodeling during T cell activation. Further, when AP-1 is inhibited, chromatin opening does not occur and T cells do not form or function correctly.
The involvement of AP-1 is important because this transcription factor also influences and overlaps with risk loci for multiple sclerosis, inflammatory bowel disease, and other allergic disease. For now, the goal for this research is understanding how the epigenome encodes T cell memory, says Artem Barski, PhD, lead investigator on the study. But downstream, this knowledge eventually may help researchers develop ways to manage pathologic immune responses, improve vaccines or find new anti-cancer immune therapies.
Researchers used ChIP-seq and ATAC-seq technologies to analyze all the protein interactions affecting chromatin state. Prior studies have focused on genetic disruptions of individual AP-1 members, but Barski’s lab developed an approach of protein electroporation, which “turned out to be amazingly efficient, delivering our dominant-negative protein into almost 100% of cells,” says first author Masashi Yukawa, PhD.
These findings have since been presented at the American Academy of Immunologists and the Cold Spring Harbor Laboratory meetings. Collaborators included researchers from the Center for Autoimmune Genomics and Etiology and the Division of Biomedical Informatics.
