Researchers identify a new gene inactivation mechanism that influences development and is related to disease

The preservation of genome integrity is essential for the proper functioning of organisms and to guarantee offspring and survival of the species. Therefore, there are various cellular mechanisms that prevent mutations and chromosomal abnormalities. However, failure of any of these mechanisms can lead to genomic instability, which is associated with a wide variety of diseases, such as ataxia telangiectasia, xeroderma pigmentosum, and cancer

Scientists led by Dr. Cayetano González, ICREA researcher at IRB Barcelona, and Dr. Renata Basto, group leader at the Institut Curie in France, have found a new form of instability, which is not genomic but functional, that they have called “ Illuminati”. This form of instability does not take place in the DNA sequence, or the structure, number, or function of chromosomes, but rather acts at the epigenetic level. The researchers have observed this phenomenon in neural (nervous system) stem cells in the brain of the Drosophila fly.

“Illuminati is unlike other epigenetic mechanisms of gene inactivation known to date in Drosophila and it is sensitive to environmental conditions such as diet and temperature. In particular, Illuminati is highly potentiated in malignant tumours that originate from Drosophila neural stem cells”, explains Dr. González.

Drosophila as a model to study genomic instability and disease

The Cell Division laboratory at IRB Barcelona uses the Drosophila fly as an experimental model to study the causes and effects of genomic instability. One of the tools they have developed consists of flies with markers designed in such a way that a fluorescent signal is turned on only in cells in which the integrity of the genome is compromised. The key to this system is a protein called Gal80, so mutations in the gene that encodes this protein (or the loss of the chromosome that carries this gene) act as molecular triggers that lead to the expression of a fluorescent protein.

This technique, which is highly sensitive since it can detect genomic instability in a single cell within an entire organism, has allowed the discovery of this new epigenetic regulation mechanism.

Among other projects, the group is currently using this study model to examine the contribution of genomic instability to tumour growth, and the differences in genomic instability between the sexes.

This study has been supported by the European Research Council (ERC), the Spanish Ministry of Science and Innovation, the European Regional Development Fund (ERDF), and the French National Centre for Scientific Research (CNRS).

Illuminati: a form of gene expression plasticity in Drosophila neural stem cells
Alix Goupil, Jan Peter Heinen, Riham Salame, Fabrizio Rossi, Jose Reina, Carole Pennetier, Anthony Simon, Patricia Skorski, Anxela Louzao, Allison J. Bardin, Renata Basto and Cayetano Gonzalez
Development (2022) DOI: 10.1242/dev.200808

About IRB Barcelona

Created in 2005 by the Generalitat de Catalunya (Government of Catalonia) and University of Barcelona, IRB Barcelona is a Severo Ochoa Centre of Excellence, a seal that was awarded in 2011. The institute is devoted to conducting research of excellence in biomedicine and to transferring results to clinical practice, thus improving people’s quality of life, while simultaneously promoting the training of outstanding researchers, technology transfer, and public communication of science. Its 27 laboratories and eight core facilities address basic questions in biology and are orientated to diseases such as cancer, metastasis, Alzheimer’s, diabetes, and rare conditions. IRB Barcelona is an international centre that hosts 400 employees and more than 30 nationalities. It is located in the Barcelona Science Park. IRB Barcelona is a CERCA center, and a member of the Barcelona Institute of Science and Technology (BIST).