In new research published in the journal Cell, researchers have found that ignored pieces of DNA play a critical role in the development of immune cells (T cells). These areas activate a change in the structure of DNA that brings together crucial elements necessary for T cell formation. The big bang discovery might support in combating diseases.
Intricate human physiological features such as the immune system require exquisite formation and timing to develop properly. Genetic elements must be activated at just the right moment, across vast distances of genomic space. Promoter areas, locations where genes begin to be expressed, must be paired precisely with enhancer clusters, where cells mature to a targeted function.
Faraway promoters must be brought in proximity with their enhancer counterparts. When these elements are not in sync, diseases such as leukaemia and lymphoma can result. The scientists called it the big bang of immune cell development and made their discovery within previously overlooked stretches of DNA located between genes.
Through genomic studies and genetic experiments in mice, the scientists found that the ignored areas, known as non-coding DNA, activate a change in the 3D structure of DNA that brings promoters and enhancers together with stunning accuracy. The team describes the mechanism as somewhat like a stiff wire with enhancers and promoters on either end that's bent together into a loop and anchored in place.
Enhancers and promoters, once distantly separated, are now repositioned in close proximity to initiate the development of immune system building blocks known as T cells. The process of architecture remodelling allows the enhancer and promoter to find each other in 3D space at precisely the right time. It is all very carefully orchestrated.
The researchers have seen one example but there are likely many others all occurring at the same time when cells are moving along the developmental pathway-that's kind of amazing. While the team concentrated on T cells, they believe this mechanism may be unfolding throughout the animal and plant kingdoms. When the mechanism fails, T cell development falters and diseases such as lymphoma and leukaemia result.
The study findings showed how the forgotten strands of DNA suppress the development of leukaemia and lymphoma. The implications of these results are not only how normal T cells develop, but that tumour suppression is regulated through this mechanism, at least in part. Ultimately we may be able to fix mutations associated with disease and these forgotten strands of DNA, the researchers said.