Map of tonsil's genetic 'spaghetti' yields insights into immunity
About 2 meters (6.6 feet) of genetic material must fit into the nucleus of each of most of our trillions of cells, coiling and winding to form what looks like a tangled mess. But when genes are used, how they are used and how often they are used are completely intertwined with that mess.
Genetic material must fit tightly within each cell's nucleus, coiling and winding to form a tangled mess. Chromosomes appear as a "spaghetti" configuration, requiring specific organization that varies between cell types. In 2019, researchers David G. Schatz and Siyuan Wang mapped the genetic spaghetti of human tonsil tissue, a key component of the immune system.
Using MINA, a novel imaging technique developed by Wang, they visualized chromosomes, DNA, RNA, and proteins within intact tissue slices. MINA reveals unique 3D genome changes in different cell types, making it the first single-cell 3D genome atlas of human tonsil and the first image-based 3D genome atlas of any human organ. Schatz and Wang discovered "hot" and "cold" regions within the genome, with the former more likely to undergo somatic hypermutation – a process that enhances antibody specificity against pathogens.
Targeting proteins that maintain 3D genome loops resulted in halting somatic hypermutation. Despite the loops disappearing, the effect on hypermutation was temporary, suggesting other factors are at play. Understanding these processes could reveal insights into pathologies like B-cell lymphomas, where hypermutation may lead to cancer-causing mutations.
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