Study highlights the darkest parts of our genetic heritage

More than half of our genome is made up of transposons, DNA sequences reminiscent of old extinct viruses. Transposons are normally silenced by a process called DNA methylation, but their activation can lead to serious diseases. Very little is known about transposons, but researchers involved in an international collaborative project have for the first time succeeded in studying what happens when methylation of DNA is lost in human cells. These results provide new insights into how changes in DNA methylation contribute to disease.

Even when our DNA is intact, the expression and behavior of our genes can change. This can occur in different ways, including via methylation of DNA, a chemical process that blocks genes and other parts of our genome, such as transposons.

Transposons, that is, jumping genes, are sometimes called the dark part of our genome and consist of transposable DNA sequences that can cause genetic changes, for example if they are integrated into a gene. gene. These transposons are often silenced during fetal development, including methylation of DNA.

"Sometimes, however, DNA methylation is interrupted and studies have shown that it is important in certain cancerous tumors and in certain neuropsychiatric diseases." DNA methylation is used as a therapeutic target. in some types of cancer, such as leukemia, but we still lack knowledge.John Jakobsson, professor at Lund University and director of the study, which also included researchers from the Max Planck Institute of Molecular Genetics and of the Karolinska Institutet, the results are now published in Nature Communications.

In fact, we know very little about the role of transposons in our DNA. Lund researchers have advanced the hypothesis that methylation of DNA would silence parts of the genome that are not being used, but it is only now that it is possible to study what happens when this process is removed from human cells.

The researchers used the CRISPR / Cas9 technique to successfully stop the methylation of DNA in human neural stem cells in the laboratory.

"The results were very surprising.If you stop DNA methylation in mouse cells, they will not survive." But when methylation of DNA was interrupted in human nerve stem cells, they survived and a specific set of transposons were activated, which in turn affected many genes that play an important role in the development of nerve cells, "says Johan Jakobsson.

Johan Jakobsson thinks that the results offer the possibility of a totally new understanding of the DNA methylation loss affecting our genome in various diseases, but he also points out that the study was conducted on cells in culture in the laboratory. The researchers now want to go ahead and see what happens if they stop methylation in cancer cells affected by DNA methylation, for example in glioblastoma.