Each cell of the human body contains two meters of DNA. The whole secret lies in the intricate three-dimensional arrangement that allows DNA strands to be efficiently organized and compacted within the cell. Packaging issues are associated with many serious diseases such as leukemia, glioma, autism, and cancer. Scientists worldwide are trying to understand exactly how specific diseases are associated with packaging disorders.
Scientists from Skoltech, the Institute of Gene Biology of the Russian Academy of Sciences, and other leading scientific organizations have also made efforts in this direction. In their new study, the researchers examined the spatial organization of chromatin, which includes DNA and related structural proteins, in one of the most interesting model organisms in biology, Dictyostelium. The transitional state of this social amoeba is intriguing, as it usually exists as separate cells, but when conditions worsen, they assemble into multicellular aggregates and differentiate. The research results are published in the Nucleic Acids Research journal.
“Dictyostelium is a unicellular creature. If there is not enough food, cells assemble into a single multicellular organism and then transform into something resembling a miniature fungus. Cells that form the cap can turn into spores and scatter to start new colonies, but those who are not fortunate enough to stay in the stem, die. This is a very interesting point of transition from unicellularity to multicellularity,” commented Vice President for Biomedical Research at Skoltech, Doctor of Sciences in biology, Professor Mikhail Gelfand, a study co-author.
Experimental data obtained by colleagues from the Institute of Gene Biology of the Russian Academy of Sciences showed that Dictyostelium has a focus of organization in the nucleus, to which all the chromosomes are attached — they come out of it in a bundle. Yeast also has the same way of organizing chromosomes, while in humans and other mammals, each chromosome occupies its own specific region in the nucleus.
“If we look at the average chromatin structures in human cells and many other organisms, we will see that chromosomes seem to be folded into clusters called topologically associated domains. This results from averaging of loops formed in separate cells. Dictyostelium does not possess these clusters, but it does have chromatin loops, which could be even more noticeable than in humans. We have studied how these loops change at different stages of the transition from the unicellular to the multicellular form,” said Ekaterina Khrameeva, Doctor of Sciences in biology, an associate professor at the Bio Center of Skoltech and a co-author of the work, a winner of the Moscow Government Young Scientist Award in 2024.
The authors discovered that the genes at the formation of these loops are oriented towards each other. The formation mechanism of these loops is most likely related to a protein, RNA polymerase, which synthesizes RNA from a DNA template. The movement of these proteins causes a loop, just as attempting to untangle a ball of thread from two ends causes a knot in the middle.