Computer simulations animate in detail how DNA opens at the atomic level.

3 microseconds from nucleosome lifespan. Snapshots in time were taken every 4 nanoseconds and overlaid on the histone (white) core region. The DNA of all snapshots and the location of the flexible histone tail are shown. The DNA is yellow and the histone tails are shown in blue, green, red, orange and cyan. Sufficient movement of the DNA arm is known as nucleosome respiratory movement. Surprisingly, in this nucleosome, the DNA sequence causes the lower arm to move more than the upper arm. Credits: Jan Huertas and Vlad Cojocaru, © MPI Münster, © Hubrecht Institute.

Researchers at the Hubrecht Institute in Utrecht (Netherlands) and the Max Planck Institute for Molecular Biomedical Sciences in Münster (Germany) used computer simulations to put short pieces of DNA around the proteins that package the DNA. The details of the atom reveal how it opens when tightly wrapped. genome. These simulations provide unprecedented insight into the mechanisms that regulate gene expression.The results will be published in the next issue PLOS Computational Biology On June 3rd.

Every cell in the body contains 2 meters of DNA. In order to put all the DNA in the small nucleus of the cell, the DNA is tightly packed in a structure known as chromatin. Chromatin is a sequence of the same small structures called nucleosomes.Single Nucleosomes, DNA is wrapped around eight proteins called histones. Chromatin is not uniformly compact throughout the genome. Package airtightness is important in regulating which genes are expressed and therefore which proteins are produced by cells.

The transition from dense DNA to loosely packed DNA (from chromatin closure to release) is essential for cells to transform into another cell type. These cell transformations are characteristic of development and disease, but are also commonly used in regenerative medicine. Understanding how these transitions occur can contribute to understanding the disease and optimizing therapeutic cell type conversion.

Computational nanoscope

The movement of DNA in a nucleosome-encapsulated state is one step in the chromatin opening. Like all the molecular structures of our cells, nucleosomes are dynamic. They move, twist, breathe, unfold, and wrap again. Visualizing these movements using experimental methods is often very difficult. One alternative is to use so-called “computational nanoscopes”.

Researchers use the term computational nanoscope to refer to a set of computers. simulation Method. These methods allow you to visualize the movement of molecules over time. In the last few years, the methods have become so accurate that researchers have begun to call them computational nanoscopes. Observing molecules moving on a computer is similar to observing molecules with a very high resolution nanoscope.

Nucleosome respiration

Jan Huertas and Vlad Cojocaru, with the help of Hans Schöler of the Max Planck Institute for Molecular Biomedicine (Münster, Germany), created multiple real-time videos of nucleosome movement, each covering 1 microsecond from nucleosome lifespan. Did. Using these videos, they monitored how nucleosomes open and close in a movement called nucleosome respiration.

In their new treatise published in PLOS Computational Biology, Weltas and Cojocaru describe the causes of nucleosome respiration. First, they discovered that the order in which the components of DNA are placed, that is, the DNA sequence, is important for the respiration of nucleosomes. Second, the dynamics of histone tails are essential to this process. These histone tails are flexible regions of histones that play a role in the regulation of gene expression. The role of histone tails has been intensively studied, but little is known about how they affect the movement of a single nucleosome. Huertas and Cojocaru used simulations to explain in detail the relationship between histone tails and nucleosome respiration at the atomic level.

Histone modification

“Being able to observe the respiration of nucleosomes Computer simulation It’s very challenging. The fact that this can now be visualized represents a major step towards simulating the complete spectrum of nucleosome dynamics, from breathing to unwrapping. You can also study how histone modifications that occur in different cells and regions of DNA affect these movements. Our simulations show that the two histone tails play a role in keeping the nucleosomes closed. Only when these flexible tails moved away from specific regions of DNA could the nucleosomes open, “says research leader Vlad Cojocaru.

Jan Huertas, lead author of this publication and a recent PhD holder, adds: Histone tail. The next step is to run the simulation with such changes. The atomic resolution of the simulation allows us to identify how each modification affects the dynamics of nucleosomes and chromatin. “

Toward understanding of epigenetics

All three researchers are excited about the future of the use of atomic computer simulation in understanding gene expression mechanisms in development and disease. “With further improvements in the computing power available in the world, we will be able to simulate the lifetime of nucleosomes containing all atoms in milliseconds. In addition, we will be able to simulate multiple nucleosomes on a daily basis. It will allow us to study the effects of various modifications, which will give us unprecedented insight into the mechanisms that regulate gene expression, “concludes Cojocaru.

A new way to analyze nucleosomes

For more information:
The histone tails work together to control the respiration of the genomic nucleosome. Jan Huertas Hans R. Schöler, Vlad Cojocaru, PLOS Computational Biology, 2021.

Provided by
Hubrecht Institute

Quote: Computer simulations animate how DNA opens (3 June 2021) with atomic details (3 June 2021, -Obtained from animate-atomic-dna.html)

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