Genome in 3D
Geneticists received the first "three-dimensional photograph" of the human genome
Molecular biologists from the USA have received the first detailed three-dimensional map of the genome, on which you can see how all known genes and sections of "junk" DNA are located inside the nucleus of a living cell. It was presented in an article in the Journal of Cell Biology (Chen et al., Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler).
"We don't yet understand why DNA is stacked in the nucleus in this way. On the other hand, it can already be said that even small shifts of chromosomes, by several hundred nanometers in one direction or the other, can greatly affect the level of gene activity," says Andrew Belmont from the University of Illinois at Urban (in the press release of Researchers develop “cytological ruler" to build a 3D map of human genome – VM).
Contrary to the ideas of ordinary people, chromosomes acquire a characteristic X-shaped shape and become clearly visible in a microscope only during cell division. During the interphase, a period of calm, they lose their shape and turn into a kind of tangle of closely intertwined threads, whose "format" of packaging and the very fact of existence arouses great interest from biologists and physicists.
This tangle, resembling in its structure a briquette of instant noodles, as suggested by Soviet scientists back in 1988, is a so–called fractal tangle - a special mathematical structure of intersecting curves, whose curls repeat, like all fractal objects, the shape of the entire chromosomal thread.
Molecular biologists, as Belmont notes, have long been trying to "unravel" it and understand why the cell packs the genetic code in this way and how various genes are located inside it, vital for the functioning of all body tissues.
His team was able to solve this problem by taking advantage of the fact that there are a large number of so–called "speckles" in the nucleus - dense spherical structures of RNA and proteins that separate individual strands of the "tangle" of chromosomes. They, as scientists believe today, play an important role in reading genes, but their exact role has yet to be revealed.
Belmont and his colleagues changed the genome of human cells in such a way that molecules of a special enzyme, horseradish peroxidase, began to accumulate inside the speckles.
He simultaneously performs two tasks – "highlights" the strands of chromosomes, oxidizing various organic compounds, and marks individual genes with the help of a tyramide, one of the molecules he produces. As a rule, the closer the gene is to the speckle, the more tyramide marks will appear on its surface.
Photo: Chen et al., 2018
Such a trick, as the biologist explains, allows not only to get an accurate three-dimensional photograph of the "tangle" of chromosomes, but also to find out which genes are at any point in this structure. To do this, it is enough to extract DNA from a cell, decipher its structure and count the number of labels on the surface of each gene.
Based on such ideas, geneticists obtained full-fledged three-dimensional photographs of chromosomes in the nucleus of cancer cells extracted from the body of people suffering from leukemia.
The first analysis of these images, as Belmont notes, unexpectedly indicated that the activity of genes does not depend on how close to the center of the nucleus they are, as indicated by past attempts to unravel the "chromosomal tangle". In fact, the most "readable" genes are located near speckles and other cavities, the reasons for which have yet to be clarified.
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