MSGID: 1:317/3 649e5a72   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    How the motion of DNA controls gene activity    
      
     Date:   
         June 29, 2023   
     Source:   
         Institute of Science and Technology Austria   
     Summary:   
         Despite being densely packed to fit into the nucleus, chromosomes   
         storing our genetic information are always in motion. This allows   
         specific regions to come into contact and thereby activate a   
         gene. A group of scientists now visualized this dynamic process   
         and give novel insights into the physical characteristics of DNA.   
      
      
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   Performing cutting-edge science requires thinking outside the box and   
   bringing together different scientific disciplines. Sometimes this even   
   means being in the right place at the right time. For David Bru"ckner,   
   postdoctoral researcher and NOMIS fellow at ISTA, all the above-mentioned   
   things came into effect as he attended an on-campus lecture by Professor   
   Thomas Gregor from Princeton University. Inspired by the talk, Bru"ckner   
   reached out with an idea: to physically interpret the specific data sets   
   Gregor presented. Now, the results of their collaboration are published   
   in Science. 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.   
      
   How DNA fits into a cell nucleus Living organisms like humans are built   
   on genes that are stored in the DNA - - our molecular blueprint. DNA is   
   a polymer, a huge molecule of smaller individual parts (monomers). It   
   is located in every cell's nucleus. "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," Bru"ckner explains. 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, which we all encountered in   
   a biology textbook.   
      
   "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," Bru"ckner 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.   
      
   Visualizing gene regions 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. Bru"ckner 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."  DNA is densely packed and   
   exhibits fast motion The challenge then was how to analyze this huge   
   data set of stochastic motion.   
      
   His background in theoretical physics allowed Bru"ckner to extract   
   statistics to understand the typical behavior of the system. He applied   
   two simplified, different physical models to cut through the data.   
      
   One was the Rouse model. It assumes that every monomer of the polymer is   
   an elastic spring. It predicts a loose structure and fast diffusion --   
   a random movement, where occasionally the gene regions encounter each   
   other. The other model is called the "fractal globule." It predicts   
   a very compact structure and therefore slow diffusion. "Surprisingly,   
   we found in the data that the system is described by a combination of   
   these two models -- a highly dense structure you would expect based   
   on the fractal globule model, and diffusion which is described by the   
   statistics from the Rouse model," Bru"ckner explains.   
      
   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," Bru"ckner adds.   
      
   This study brings together the worlds of biology and physics. For   
   physicists, it is interesting, because the scientists tested the dynamics   
   of a complex biological system with physical theories that have been   
   around for a long time; and for biologists, it gives insights into the   
   characteristics of a chromosome, which might help to understand gene   
   interaction and gene activation in more detail.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Genes # Gene_Therapy # Human_Biology # Epigenetics   
             o Plants_&_Animals   
                   # Genetics # Biochemistry_Research # Biotechnology #   
                   Cell_Biology   
       * RELATED_TERMS   
             o Telomere o DNA_microarray o Genetics o DNA o Chromosome o   
             Meiosis o Allele o Gene   
      
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   Story Source: Materials provided by   
   Institute_of_Science_and_Technology_Austria. Note: Content may be edited   
   for style and length.   
      
      
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   Journal Reference:   
      1. David B. Bru"ckner, Hongtao Chen, Lev Barinov, Benjamin Zoller,   
      Thomas   
         Gregor. Stochastic motion and transcriptional dynamics of pairs   
         of distal DNA loci on a compacted chromosome. Science, 2023; 380   
         (6652): 1357 DOI: 10.1126/science.adf5568   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/06/230629193228.htm   
      
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