Tech/Science

Groundbreaking Discovery Reveals Critical Role of DNA Loops in Gene Repression

USC Stem Cell scientists have made a groundbreaking discovery that could reshape our understanding of how DNA functions and influences human health. The study, led by Oliver Bell, revealed the critical role that DNA loops play in gene repression. Published in Nature Communications, the research provides insight into the organized loop structures in DNA, which connect distant sections of the genome and serve as a key regulator of gene activity.

Oliver Bell’s team, including first author Daniel Bsteh, centered their research on developmental genes that are suppressed by Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). These complexes prevent the untimely or incorrect activation of developmental genes, which can lead to severe developmental defects or cancer.

The team’s research, conducted in mouse embryonic stem cells, identified a protein named PDS5A that can alter these loops without interfering with histone modifications. This discovery allows for the isolated study of loops and 3D genome organization on gene silencing.

When the team disrupted PDS5A, they found that it had a significant effect on the loops and led to normally silent genes becoming aberrantly active. This discovery suggests that the cohesin complex, of which PDS5A is a member, is vital for maintaining the 3D organization of the genome. Moreover, mutations in cohesin could lead to diseases such as cancer and developmental disorders.

The findings will likely have a profound impact on our understanding of gene regulation and disease development. The study received support from the Austrian Academy of Sciences, the New Frontiers Group, the Human Frontiers Science Program, and the USC Norris Comprehensive Cancer Center. The implications of this research may well extend to the development of new diagnostic tools and treatments for cancer and other disorders linked to developmental genes.

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