Reverse engineering 3D chromosome models for individual cells

Date:
January 14, 2021
Source:
University of Illinois at Chicago
Summary:
A new computational technique that uses heat map data to reverse
engineer highly detailed models of chromosomes and researchers have
uncovered new information about the close spatial relationships
that chromatin folding creates between genes.



FULL STORY ========================================================================== Genome analysis can provide information on genes and their location on
a strand of DNA, but such analysis reveals little about their spatial
location in relation to one another within chromosomes -- the highly
complex, three- dimensional structures that hold genetic information.


========================================================================== Chromosomes resemble a fuzzy "X" in microscopy images and can carry
thousands of genes. They are formed when DNA winds around proteins --
called histones - - which are further folded into complexes called
chromatin, which make up individual chromosomes.

Knowing which genes are located in spatial proximity within the chromatin
is important because genes that are near each other generally work
together.

Now, researchers at the University of Illinois Chicago report on a computational technique that uses heat map data to reverse engineer highly detailed models of chromosomes. Through this work, the researchers have uncovered new information about the close spatial relationships that
chromatin folding creates between genes that can be highly distant from
one another along DNA strands.

Their findings are published in the journal Nature Communications.

"Folding of the chromatin brings genes that are far away from each
other into close proximity. If we know that certain groups of genes
are spatial neighbors because of this folding, that tells us they most
likely work together to drive processes such as the development of
immunity, or even more fundamental processes like development or cell differentiation," said Jie Liang, UIC Richard and Loan Hill Professor
of Bioengineering and a corresponding author on the paper. "This is
important for better understanding these processes or development
of new therapeutics to prevent or treat cancer and other diseases."
Liang and his colleagues developed a way to reverse engineer the complex structures of individual chromosomes using information from a process
called Hi-C. Hi-C generates heat maps based on probabilities reflecting
which genes are most likely to be spatially close to one another. These
heat maps can provide approximate three-dimensional information on how chromosomes are organized, but because they are based on genetic material
from multiple cells, the maps represent average likelihoods of proximity between genes, not exact locations.

Liang and colleagues looked at Hi-C heat maps of chromosomes from cells
of fruit fly embryos, which have only eight chromosomes. They used
these heat maps together with new advanced computational methods to
generate extremely detailed three-dimensional maps of the chromosomes
of individual cells.

"For the first time, we are able to produce single-cell models that
accurately represent genetic spatial relationships within chromosomes,"
Liang said. "With these models, we can uncover rich biological patterns
and answer basic biological questions about three-dimensional structural changes chromosomes undergo to cause stem cells to develop into different tissues, and how malfunctions in these processes lead to diseases such
as cancer."

========================================================================== Story Source: Materials provided by
University_of_Illinois_at_Chicago. Original written by Sharon
Parmet. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Qiu Sun, Alan Perez-Rathke, Daniel M. Czajkowsky, Zhifeng Shao, Jie
Liang. High-resolution single-cell 3D-models of chromatin ensembles
during Drosophila embryogenesis. Nature Communications, 2021; 12
(1) DOI: 10.1038/s41467-020-20490-9 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/01/210114134030.htm

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