Supercomputer reveals how the X chromosome is folded and inactivated

Using supercomputer-driven dynamic modeling based on experimental data, researchers can now explore the process of closing an X chromosome in female mammalian embryos

"This is the first time we have been able to simulate all RNA that spreads around chromosomes and shuts them down," said a visiting scientist at Los Alamos National Laboratory, Massachusetts General Hospital and Harvard.

This model is considered four-dimensional because it shows movement, including time in the fourth dimension, and it runs on the Los Alamos supercomputer

In visualization, RNA particles are clustered on the X chromosome

Jeannie T.

Epigenetics is the study of gene expression and genetic trait changes that do not involve mutations in the genome

Li said: "What this field lacks is a way to allow users who are not good at computing to interact with chromosomes

Based on the work summary Los Alamos is currently developing a Google Chrome Earth->

In mammals, a female embryo has two X chromosomes, one inherited from the parents

Lee said the new Los Alamos model will promote a deeper understanding of gene expression and related issues, which may lead to drug treatments for various genetic diseases and disorders

"Our main goal is to observe changes in the shape of chromosomes and changes in gene expression levels over time," Sanbonmatsu said

Sanbonmatsu said that to understand how genes turn on and off, “understanding the structure of chromosomes is really helpful

Li compared the structure of chromosomes to "origami

The model shows various substructures in chromosomes

The model also showed that genes on the chromosome surface escaped X chromosome inactivation, confirming early experimental work
.
In the model, they are clustered on the surface of chromosomes, apparently interacting or working together
.

In another point of view of the model, "When the chromosome goes from an active X, when it is still quite large, to a compact inactive X, which is smaller, we noticed that there is a very dense core of the chromosome.
, But the surface density is much smaller
.
We also see more movement on the surface," Lapala said
.
"Then there is an intermediate region, which is not too fast or slow, where the chromosomes can be rearranged
.
"

The inactive protein X is then activated in a process called "age-related inactive protein X activation
.
" "Some studies have tried to pharmacologically activate the inactive X chromosomes and give them what is missing on the active X chromosomes to treat children's neurological diseases
.
For example, a child may have a mutation
that causes the disease .
We believe that if We can reactivate the normal copy of the inactive X chromosome, and then we can perform epigenetic treatment of this mutation
.
"

Original search:

"4D chromosome reconstruction elucidates the spatial reorganization of the mammalian X-chromosome," in Proceedings of the National Academy of Sciences.
Anna Lappala, Chen Yu Wang, Andrea Kriz, Hunter Michalk, Kevin Tan, Jeannie Lee, and Karissa Sanbonmatsu.
An embargo copy is available from  PNAS  through  https:// .