Geni, discovered a new organizational model.
Scientists discover new organizational principles of the genome, between stresses and hydrodynamics.
A team of scientists has discovered the physical principles – a series of hydrodynamic forces and flows – that help ensure that the ‘footprint of life’ functions properly. These results provide new insights into the genome and potentially offer a new means of identifying genomic aberrations linked to human developmental disorders and diseases.
“How the genome is organized and packaged within the nucleus directly affects its biological function , but the physical principles underlying this organization are far from being understood,” explains Alexandra Zidovska, a professor in the Department of Physicist from New York University and author of the article, published in the journal Physical Review X (PRX). “Our results provide fundamental insights into the biophysical origins of genome organization within the cell nucleus.” “This knowledge is critical to understanding genome function,” adds David Saintillan, a professor in the Department of Mechanical and Aerospace Engineering at the University of California and co-author of the study.
In particular, the research group focused on the role of the nucleoplasm – the fluid in which the genome is immersed – and on the forces that determine its organization. Specifically, they examined the forces applied by enzymes on chromatin , the substance that makes up the cell nucleus of all eukaryotic cells. These forces initiate processes, such as transcription, and act to influence the spatial arrangement of chromatin. However, despite the crucial role of this process in the transmission of genetic information, the underlying physics is unclear.
To better understand this dynamic, scientists have focused on the compartmentalization of the genome into its major parts, the euchromatin and heterochromatin . Euchromatin predominantly contains genes that actively transcribe and drive gene expression; heterochromatin contains genes that are silenced and therefore not expressed in the cell.
To capture this, the researchers created a computer modeling system that reproduces this process through a series of simulations. In their model of the nucleus, 23 chromatin fibers – the number of chromosomes in the human genome – were modeled as floating chains and inserted into a fluid-filled sphere. Each chain has been divided into active regions, or euchromatin, and passive heterochromatic regions. They found that when active forces act on the chromatin fiber, they generate flows in the fluid, which in turn affect movement and positioning of the surrounding chromatin. These forces push on the euchromatic parts and drive fluxes that cause an important spatial rearrangement of the genome, especially leading to the formation of heterochromatin compartments.
“The euchromatic, or active, parts push the heterochromatic, or inactive, parts out of their way and group them together,” Zidovska explains. In this way, the cell effectively stores inactive genes”. “This is crucial for our health: if this process goes wrong, the body doesn’t form properly and can lead to developmental disorders and other diseases, such as the development of cancer cells.” In the video, produced by the researchers, the nucleus of the cell is represented, full of chromosomes illustrated with different colors. The arrangement of chromosomes is influenced by the forces acting on the genome and their hydrodynamic interactions. (Credit: Achal Mahajan, UC San Diego)