Jul 21, 2019 | Updated: 09:46 AM EDT

Scientists Unlock the Organizational Structure of DNA

Jul 02, 2019 10:17 AM EDT

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University of California researchers ventured into finding out the organization of DNA inside the living cell. Current knowledge show that the DNA strands measure about two meters or about six feet. Present information also show that the DNA strands fold into and move within the cell nucleus the size of about a hundredth of a millimeter. However, Science has not provided information regarding the state of matter on how this happens. 

The researchers based their research on the principles of phase transitions and polymer physics. Their findings were published in the journal Nature Communications. Their results showed that the genomic DNA's phase state is a gel somewhere between the the phase boundary of gel and sol, the solid-liquid phase transition. 

Scientists explain that the "sol-gel" phase transition of the genomic DNA is similar to the consistency of pudding, panna cotta, or porridge. This demonstrates that the genomic interaction timings lead gene expression and somatic recombination. 

"This finding points to a general physical principle of chromosomal organization, which has important implications for many key processes in biology, from antibody production to tissue differentiation," said Olga Dudko, a theoretical biophysicist and professor in the Department of Physics at UC San Diego, who collaborated with colleague Cornelis Murre, a distinguished professor in the Section of Molecular Biology, on the study.

Other lead authors include Yaojune Zhang, a Princeton University postdoctoral research and former graduate student of Dudko as well as Nimish Khan na, Murre's postdoctoral scholar. They collected and analyzed DNA motion data inside live mammalian B-cells from mice to understand how remote genomic interactions produce a diverse pool of antibodies by the adaptive immune system. 

Groups of variable (V), diversity (D), and joining (J) segments are the bases of categorization of immunoglobin gene segments in mammals that include humans and rodents. The random combination of these segments occur via somatic recombination. This step happens before antigen contact and during B-cell development in the immune system's lymphoid tissue, or bone marrow. Diverse protein codes that pair antigens that activate lymphocytes are produced through these random genetic interactions. 

The researchers studied the different interactions between V, D, and J gene segments. There is still a large knowledge gap when it comes to explaining these interactions. The UC San Diego scientists formulated a process on how to track V and DJ motion in B-lymphocytes. They discovered that these segments can only move locally. 

"By comparing experimental and simulated data, the scientists concluded that constrained motion is imposed by a network of cross-linked chromatin chains, or a mesh of bridges between the DNA strands that are characteristic of a gel phase. Yet, the amount of these cross-links is "just right" to poise the DNA near the sol phase--a liquid phase describing a solution of uncross-linked chains," according to Eureka Alert.

"We have rigorous theories from physics--abstract principles and mathematical equations. We have state-of-the-art experiments on biology--innovative tracking of gene segments in live mammalian cell nuclei," noted Zhang. "It really amazes and excites me when the two aspects merge coherently into one story, where physics is not just a tool to describe the dynamics of gene segments, but helps to pinpoint the physical state of the genome, and further sheds light on the impact of the physical properties of this state on its biological function."

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