Genome complexity: 3-D relationships most important (Introduction)

by David Turell , Friday, June 30, 2023, 18:18 (302 days ago) @ David Turell

DNA is constantly in motion:

https://www.sciencedaily.com/releases/2023/06/230629193228.htm

"They highlight the stochastic (random) motion of two specific gene elements on a chromosome, which have to come into contact for the gene to become active in 3D space.

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"'Despite being heavily condensed, chromosomes are not static; they are jiggling around all the time," the physicist continues. These dynamics are very important. 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.

"Depending on the organism, the enhancer and promoter can be quite far from each other on the chromosome. "With previously used methods, you could get a static view of the distance between these elements, but not how the system evolves over time," Brückner explains. Intrigued by this missing information, the scientists set out to get a dynamic look at how these elements are organized and how they move in 3D space in real time.

"To achieve this goal, the experimental scientists from Princeton established a method to track those two DNA elements over a certain time period in a fly embryo. 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. Brückner excitedly adds, "We got a visual readout of when the enhancer and promoter got in contact. That gave us a lot of information about their trajectories."

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"Due to the combination of dense packing and fast motion, the binding of these two gene regions depends much less on their distance along the chromosome than previously anticipated. "If such a system is in a fluid and dynamic state all the time, long-distance communication is much better than we might have thought," Brückner adds."

Comment: it is not distance along the chromosome, but the 3-D relationship from the movements of DNA.