How The Motion of DNA Controls Gene Activity
Published:07 Sep.2023    Source:Institute of Science and Technology Austria
Living organisms like humans are built on genes that are stored in the DNA -- our molecular blueprint. Depending on the organism, the DNA polymer can be up to meters long, yet the size of the nucleus is on the order of microns. To fit into the tiny nucleus, DNA gets compacted by being coiled as if on a spool and further compressed into the well-known shape of chromosomes. Despite being heavily condensed, chromosomes are not static; they are jiggling around all the time. Whenever a specific gene has to be activated, two regions on the polymer called "enhancer" and "promoter" need to come into close contact and bind to each other. Only when this happens, a cellular machinery reads off the gene's information and forms the RNA molecule, which eventually gives rise to proteins that are essential for all the processes a living organism requires.
Through genetic manipulation, the DNA elements were fluorescently labeled, with the enhancer region illuminating in green and the promoter in blue. Using live imaging (time-lapse microscopy of living cells) the scientists were able to visualize the fluorescent spots in fly embryos to see how they were moving around to find each other. Once the two spots came into proximity, the gene was activated and an additional red light turned on as the RNA was also tagged with red fluorophores. The challenge then was how to analyze this huge data set of stochastic motion. Researcher Brückner extract statistics to understand the typical behavior of the system. He applied two simplified, different physical models to cut through the data.
They found that it folds into a shape that has at its center a four-way junction of DNA, of a type never seen before, enclosing the fluorophore in a way that activates it. They also observed that lettuce's foldings are held together with bonds between nucleobases -- the building blocks of DNA that are often referred to as the "letters" in the four-letter DNA alphabet. "What they have discovered is not DNA trying to be like a protein; it's a DNA that is doing what GFP does but in its own special way. Studies like this are going to be essential for the creation of new DNA-based tools. One was the Rouse model. It assumes that every monomer of the polymer is an elastic spring. The other model is called the "fractal globule." It predicts a very compact structure and therefore slow diffusion. For biologists, it gives insights into the characteristics of a chromosome, which might help to understand gene interaction and gene activation in more detail.