Researchers have discovered that the Elys protein helps to properly “pack” chromosomes into the nucleus. Previously, it was thought that only Lamins were responsible for gene stacking, and that any disruption in their function could cause premature aging syndrome, an incurable genetic disease. It turns out that Elys attaches inactive parts of chromosomes to the nuclear envelope and activates the “working” regions in the central part of the nucleus. A better understanding of the chromosome stacking process and the underlying proteins will help in the search for drugs against premature aging. The results of the study, which was supported by grants from the Russian Science Foundation (RSF), were published in Communications Biology.

In the nuclei of living cells, chromosomes are arranged in a specific way: for example, the regions containing active genes are most often located in the central part of the nucleus, while “silent” sequences are concentrated near the nuclear envelope. The proper distribution of chromosomes in space is facilitated by Lamins — proteins that interact with inactive DNA regions and pull them toward the nuclear envelope. Studies show that chromosome mis-arrangement leads to various diseases. For example, mutations in Lamins cause premature aging, resulting in a reduced life expectancy of 13 years or less. Lamins are generally associated with aging because they degrade with age. Therefore, studying the proteins that ensure proper chromosome organization may help find ways to combat premature aging.

Biologists from the Skolkovo Institute of Science and Technology and their colleagues have discovered that chromosomes are attached to the nuclear envelope by Elys, and not only by Lamins. Elys has been known to reside in the nuclear envelope and help various compounds, such as RNA and proteins, move between the nucleus and the rest of the cell. However, some studies suggested that Elys might also bind to chromosomes. This led the researchers to propose that Elys, together with Lamins, may attach DNA to the nuclear envelope and thus participate in genome 3D folding.

The team studied the functions of Elys in the cells of Drosophila melanogaster, commonly known as the fruit fly, and knocked out the gene responsible for synthesizing Elys in the fly’s salivary gland cells. The researchers then compared chromosome packaging in Elys-deficient nuclei with cells containing the fully functional protein.

It turned out that in the absence of Elys, chromosomes normally attached to the nuclear envelope “break away” and flock to the nucleus center. This confirms the notion that Elys binds DNA to the envelope. Both the chromosome parts that bind to Lamins and the DNA held by Elys near the nuclear envelope were inactive, suggesting that Elys helps to place “silent” genes away from the nucleus center.

However, further analysis showed that Elys is not only found in the nuclear envelope but also in the central parts of the nucleus, where it binds to the active sites of DNA. It may have another function here, helping to unfold the chromosome for easier gene reading.

“In this study, we have shown that Elys plays an important role in chromosome organization in the nucleus. Until recently, its role was poorly understood. Since disruptions in the function of Lamins lead to serious and as yet incurable diseases associated with premature aging, we can hypothesize by analogy that Elys may also be associated with equally serious diseases. We still need to establish this link in our further research,” says Ekaterina Khrameeva, an associate professor at the Bio Center and a participant in the projects supported by RSF grants.

Other organizations involved in the study include the National Research Center Kurchatov Institute, the Institute of Gene Biology of RAS, and Lomonosov Moscow State University.