Genetic tweaks manipulate DNA’s loops

Engineering genome shape in nucleus could influence gene activity

DNA folds

BENT INTO SHAPE  A strand of DNA folds into globules (pink and blue) as it threads through two bundles of proteins called extrusion complexes (yellow), this new simulation shows. 

Najeeb Marc Tarazi, Adrian Sanborn, E.L. Aiden

By tweaking parts of the genome, scientists have changed how DNA crams itself into a cell’s nucleus. The 3-D shape of DNA’s packaging is called the nucleome, and the structure has big implications for how genes work (SN: 9/5/15, p. 18). By changing the shape of looping DNA with a little bit of genome pruning, scientists have a new way to influence gene behavior.

In earlier work, Erez Lieberman Aiden of Baylor College of Medicine in Houston and colleagues figured out that a specific stretch of DNA acts as a stop sign that sits at the ends of the loops DNA forms as it folds. Now, by changing those signals, the researchers could move, destroy and create loops, the team reports online the week of October 19 in the Proceedings of the National Academy of Sciences.

Simulations reveal how these loops might form. Like backpack straps getting cinched up, DNA spools through a buckle formed by several proteins, Aiden and colleagues report. As the DNA feeds through this buckle, the resulting slack forms a loop that can fold around on itself as the strand grows longer and longer.

The ability to engineer loops might offer new insights into disorders that result from DNA misfolding, as well as new ways to change the ways genes behave, the researchers say. 

LOOP DE LOOP    DNA forms loops as it packs into a nucleus, a process explained here by Adrian Sanborn, a coauthor on the study.

Aiden Lab

Laura Sanders

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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