Combining lab data with supercomputing power reveals role of and chromosome structure in regulating gene expression.
Using supercomputer-driven dynamic modeling based on experimental data, researchers can now probe the process that turns off one X chromosome in female mammal embryos. This new capability is helping biologists understand the role of RNA and the chromosome’s structure in the X inactivation process, leading to a deeper understanding of gene expression and opening new pathways to drug treatments for gene-based disorders and diseases.
“This is the first time we’ve been able to model all the RNA spreading around the chromosome and shutting it down,” said Anna Lappala, a visiting scientist at Los Alamos National Laboratory and a polymer physicist at Massachusetts General Hospital and the Harvard Department of Molecular Biology. Lappala is first author of the paper published on October 4, 2021, in the Proceedings of the National Academy of Sciences. “From experimental data alone, which is 2D and static, you don’t have the resolution to see a whole chromosome at this level of detail. With this modeling, we can see the processes regulating gene expression, and the modeling is grounded in 2D experimental data from our collaborators at Massachusetts General Hospital and Harvard.”
The model—considered 4D because it shows motion, including time as the fourth dimension—runs on Los Alamos supercomputers. The model also incorporates experimental data from mice genomes obtained through a molecular method called 4DHiC. The combined molecular and computational methodology is a first.
In the visualization, RNA particles swarm over the X chromosome. The tangled-spaghetti-like strands writhe, changing shape, then the particles engulf and penetrate the depths of the chromosome, turning it off. See the visualization here:
“The method allows us to develop an interactive model of this epigenetic process,” said Jeannie T. Lee, professor of Genetics at Harvard Medical School and vice chair in molecular biology at Massachusetts General Hospital, whose lab contributed the experimental data underpinning the model.
Epigenetics is the study of changes in gene expression and heritable traits that don’t involve mutations in the genome.
“What’s been missing in the field is some way for a user who’s not computationally savvy to go interactively into a chromosome,” Lee said. She compared using the Los Alamos model to using Google Earth, where “you can zoom into any location on an X chromosome, pick your favorite gene, see the other genes around it, and see how they interact.” That capability could lend insight into… Brinkwire News Summary.