Statistical modeling paves the way for a unified DNA folding theory

The “movement” properties of single genes (points in the figures) in 3D and 2D representations. The presence of very “highly variant” genes in the two components of movement (HRG2, HRG3) is the signature of an efficient phase transition leading to cell differentiation. Credit: Alessandro Guiliani

Measuring over 2 meters in length, the human DNA molecule uses complex folding patterns to integrate into cells while locally unfolding to express genes. Such phenomena, however, are difficult to measure experimentally, and the theoretical frameworks that explain them continue to disagree with each other.

Researchers in Italy, Japan and Poland are seeking to lead the way towards a unified theory of how DNA changes shape during gene expression. Present your work in Biophysics Opinion, scientists use an approach called statistical mechanics to explore the phenomenon of so-called expression waves of gene regulation.

The group hopes to bridge a long-standing divide between the two scientific fields most affected by the subject.

“Many researchers at the intersection of physics and biology are now tackling what is arguably the most crucial puzzle in biology,” said co-author Alessandro Giuliani. “How is it possible that from the same genetic background in the fertilized egg, about 400 highly differentiated cell types can emerge, each with a specific physiological role?”

Theories based on biology often focus on regulatory proteins, called transcription factors, which biochemically drive a symphony of genes to be expressed together. In contrast, many physicists have focused on expression waves, the rhythmic changes in expression levels across the genome, driven by the relaxation and condensation of the DNA molecule itself.

“It is something like what is called the hola, common in football and other sporting events, in which spectators stand up simultaneously, causing a ‘wave’ that spreads throughout the stadium,” he said. said Giuliani.

To get to the heart of the matter, the group is focusing on a specific cell type found in breast cancer with a proven track record of consistently behaving similarly to stimuli.

They used statistical mechanics to make sense of how DNA molecules fold up by evaluating the collective behavior of a large number of microscopic actors in terms of overall properties, unlike classical top-down perspectives, such as Newton’s laws.

Ultimately, the researchers landed in favor of expression waves, recognizing that while transcription factors play a vital role, they are the second fiddle in the changing form of DNA.

To unify these two perspectives, the authors present their conclusion using concepts common to biology and physics, limiting the use of mathematics to intuitive approaches such as recurrence quantification analysis and the classical statistical method of principal component analysis.

Then they seek to apply the same approach to identify ecological tipping points based on species composition in particular habitats.

Researchers identify missing ‘switch’ that controls essential genes

More information:
“Self-organization of the expression of the whole gene by the structural transition of the coordinated chromatin” Biophysics review, 2021.

Provided by the American Institute of Physics

Quote: Regulatory Proteins or Gene Symphonies: Statistical Modeling Paves the Way for a Unified Theory of DNA Folding (2021, September 21) Retrieved September 21, 2021 from proteins-symphonies-genes-statistical -théorie.html

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