How DNA replication controls gene function. Although packed together to fit into space, chromosomes store our genetic information that is always on the go. This allows certain regions to come into contact and activate genes. A group of scientists from the Austrian Institute of Science and Technology (ISTA), Princeton University and the Institut Pasteur in Paris have now discovered this complex process and gained new insights into the physical properties of DNA., Real-time DNA organization.
Doing critical science requires thinking outside the box and combining different scientific methods. Sometimes, that even means being in the right place at the right time. For David Brückner, a postdoctoral researcher and NOMIS fellow at ISTA, everything mentioned above came into force when he attended a lecture on campus by Professor Thomas Gregor of Princeton University.
An inspired teacher, Brückner came up with an idea: to physically explain exactly what Gregor’s data showed. Today, the results of their collaboration are published in Science. They reflect the stochastic (random) movement of two specific genes on a chromosome, which must come into contact for the genes to function in 3D space.
How does DNA fit into the cell nucleus?
Human beings are built on genes stored in DNA, our molecular fingerprint. DNA is a polymer, a large molecule made up of individual subunits (monomers). It is in the nucleus of every cell. Brückner explains: “Depending on the material, the DNA polymer can be several meters long, but the size of the hole is in the order of microns.”
In order to fit into that small space, the DNA is bound together by coiling it up like a spool and then it is put into the familiar shape of chromosomes, which we have all seen in biology books. “Although they are highly compacted, the chromosomes do not change; they are always shaking,” the scientist continued.
These conditions are very important. Every time a specific gene should be injected, two regions of the polymer called “enhancer” and “promoter” will come closer and connect to each other. Only when this causes the cellular machinery to read the information from the genes and produce RNA molecules, which eventually lead to the proteins that are necessary for all the biological processes required.
Depending on the organism, amplification and amplification can be very different from the chromosome. Brückner explains: “With the methods that have been done before, you can see the distance between these things, but not about the evolution of the system over time.” Intrigued by this missing information, scientists began to look more closely at how these objects are organized and how they move through 3D space directly.
Distance of the genetic region
To achieve this goal, experimental scientists at Princeton have developed a method to track these two pieces of DNA simultaneously in fly embryos. In genetics, the DNA elements are called fluorescent, and the promoter region lights up in green and the promoter in blue. Using live imaging (accelerated microscopy), scientists can visualize fluorescent spots in embryos to see how they go about finding each other. Once the two spots are close, the gene is illuminated with red light plus the RNA also has red fluorophores. Brückner adds enthusiastically, “We have a visual check when the user and the promoter come into contact. This gave us a lot of information about their situation.
DNA is large and exhibits rapid movement
The challenge then is how to analyze this large amount of stochastic movement data. His background in theoretical physics allowed Brückner to develop statistics to understand the behavior of the system. He put two different types, easy to cut the data.
One is the Rouse model. It assumes that every monomer in the polymer is a fluid. It predicts loose patterns and rapid diffusion – random movement, where sometimes genetic regions overlap. The other principle is called “fractal globule”. It predicts a very compact structure and therefore spreads easily.
“Surprisingly, we found that the data describes the process by a combination of these two models – a very large process that one would expect based on the fractal globule model, and the diffusion that is described by and figures from the Rouse model.” Brückner said.
Due to the combination of high density and rapid movement, the association of these two genetic regions is less dependent on their distance along the chromosome than previously expected. “If such a system is in the water and the conditions are always strong, the long-term communication is better than we thought,” Brückner adds.
Source: Institute of Science and Technology Austria
