Temporarily disabling a protein complex that organizes DNA into loops inside the cell’s nucleus drastically disrupted the three-dimensional structure of the genome, but surprisingly most genes continued to function as usual, Weill Cornell Medicine researchers found. However, they also discovered a small group of affected genes that play a critical role in guiding cells to become specific types, for example heart, brain, or liver cells.
The study, published April 13 in Nature Genetics, helps resolve a long-standing paradox in biology about genome architecture and cell function, which may provide insights into certain developmental disorders and cancers.
The protein complex, called cohesin, plays a key role in shaping the three-dimensional structure of DNA inside the nucleus. This organization not only helps DNA fit inside the nucleus but brings distant regulatory elements into contact with the genes they control, influencing which genes are turned on or off to maintain cell identity and function.
Intriguingly, previous research suggested that removing cohesin—and the loops it forms—had little effect on overall gene activity. At the same time, mutations in cohesin are commonly found in cancers and in disorders, known as cohesinopathies, that affect physical and cognitive development.
