Researchers from the Institute of Gene Biology of the Russian Academy of Sciences and their international counterparts have identified a novel protein named Vostok in the brain of the fruit fly (Drosophila). This protein is instrumental in regulating the spatial arrangement of DNA within neurons and could serve as a valuable tool for treating inherited neurological conditions. This discovery was reported by the Russian Science Foundation (RSF).
The protein uncovered by the researchers binds to specific segments of DNA, creating loops. These loops are vital for the proper functioning of genes, particularly those that govern the development of the nervous system.
As noted by experts at the science foundation, the DNA within cell nuclei possesses an intricate three-dimensional structure that influences the activity level of various genes. However, the precise method by which the formation of DNA loops is controlled – loops that allow regulatory proteins to approach target genes and thus modify their activity – remained incompletely understood.
Through computational analysis, scientists from the Institute of Gene Biology (Moscow) and Princeton University (USA) discovered a short, repeating sequence within the genome of Drosophila neurons. This sequence is frequently found in areas believed to be involved in loop formation, and they confirmed that the new protein binds to it.
Schematically, DNA loops are depicted as an arc, resembling the trajectory of a rocket. Consequently, the researchers named the new protein Vostok, in honor of the first piloted spacecraft.
To determine the protein`s functions, the scientists employed the CRISPR-Cas9 gene-editing technique to generate mutant larvae in which the Vostok gene was deactivated. It was observed that the DNA in these Drosophila had seven percent fewer loops.
«Our research confirms that the three-dimensional folding of DNA is strictly controlled by DNA-binding proteins, and Vostok turned out to be one of them,» stated Maxim Erokhin, head of the chromatin biology group at the Institute of Gene Biology of the Russian Academy of Sciences, as quoted in the report.
According to Erokhin, understanding how loops form in the DNA molecule opens up new opportunities for gene therapy. For instance, by comprehending how to manipulate loop formation, scientists might be able to correct gene function in cases of hereditary nervous system diseases in the future.
«Since mutations in the Vostok and GAF genes lead to the loss of only about 15 percent of DNA loops, other proteins with similar properties must exist in the Drosophila genome. Searching for such proteins is one of our future tasks,» the report cites Darya Chetverina, head of the epigenetics group at the Institute of Gene Biology of the Russian Academy of Sciences.
Looking ahead, the scientists also intend to explore the possibility of directed creation of DNA loops using the Vostok protein when it is produced in human cells.
The findings of this research, supported by a grant from the Russian Science Foundation (RSF), have been published in the journal Molecular Cell.
