The secrets of folding DNA

- EN - DE- FR- IT
By studying the neurons of flies, geneticists at the University of Lausanne have
By studying the neurons of flies, geneticists at the University of Lausanne have discovered novel folds in the DNA (colored threads here): meta-loops. Specific zones (here the wooden beads), yet far apart on the DNA thread, interact. Labo Gambetta, CIG-UNIL

A study published on August 2, 2023 in "Cell" by a team from the University of Lausanne reveals that the way DNA folds back on itself directly influences the development and functioning of the nervous system.

DNA is like a thread of wool which, during development, twists around itself to form a chromosome, a ball of yarn. The team led by Maria Cristina Gambetta, Associate Professor at the Centre intégratif de génomique (CIG) in the Faculty of Biology and Medicine at the University of Lausanne, has discovered a new type of fold specifically in neurons. Called meta-loops, they correspond to loops that form when two specific regions far apart on the DNA strand - sometimes at the two ends of a chromosome - come into contact.

Mammals, including mice and humans, have similar genetic architectures, but due to the great complexity of these organisms, it has never been possible to determine the role played by these structures," reports Maria Cristina Gambetta, director of the study published August 2 in Cell and carried out in collaboration with EPFL and the universities of Princeton and Warsaw.

Using a simpler model - the vinegar fly (Drosophila melanogaster) - the team was able to demonstrate that meta-loops have a particular function: they influence DNA reading during the development of the flies’ nervous system. By deleting these genetic loops, the researchers observed a connection problem between the insects’ brains and muscles, resulting in coordination difficulties and convulsions.

Genetic partners reunited

These meta-loops are very large structures, some of them about an eighth the length of the entire genome - at least in flies. No known DNA folding mechanism can explain their formation, but scientists at the University of Lausanne have shown that at least some of them are created when particular proteins bind to DNA located at anchors (the two distant regions on the DNA ribbon that come into contact).

The most remarkable and surprising aspect of the meta-loops we have discovered is the specificity with which the DNA at the two anchors interacts despite the enormous distances separating them on the genetic thread", stresses the professor. Her research group is currently investigating how these attachments communicate ’at a distance’ so as to be able to join up during nervous system development.

Meta-loops offer a whole new paradigm to explore, a novel way of approaching the difficult task of understanding DNA. The ball of genetic yarn is far from being fully unwound, and has yet to reveal all its secrets", concludes the researcher.