SEP 06, 2019 06:54 PM PDT

A 3D Look at the Genome Reveals a Super Enhancer

WRITTEN BY: Carmen Leitch

We can write out the sequence of the genome, but the three-dimensional structure of the molecule is important to its function as well. Now researchers at St. Jude Children's Research Hospital have generated a three-dimensional map of the mouse genome for the first time. Their work has revealed new insights into how the genome is organized and what it does during development, which can help us learn more about human developmental disorders. The findings have been reported in Neuron.

St. Jude scientists have used a 3D genome to improve understanding of gene regulation during development and disease. Pictured here, left to right, are Jackie Norrie, Ph.D.; Marybeth Lupo, Ph.D.; and Victoria Honnell, a graduate student, who work in the lab of Michael Dyer, Ph.D. / Credit: St. Jude Children's Research Hospital

"Understanding the way cells organize their genomes during development will help us to understand their ability to respond to stress, injury and disease," said Michael Dyer, Ph.D., chair of the St. Jude Department of Developmental Neurobiology and a Howard Hughes Medical Institute investigator.

In this work, the scientists concentrated on the genomes contained in the nuclei of rod cells in the mouse retina, which sense light. As the retina develops in the mouse, over 8000 genes are activated or deactivated, and thousands of expression regulators are involved. Using a technique called ultra-deep chromosome conformation capture or Hi-C analysis, the researchers were able to make a map of the interactions between regulators and genes in mouse rod cells.

The organization of the genome was found to be changing in surprising ways at various developmental stages. "These changes are not random, but part of the developmental program of cells," noted Dyer.

The researchers also identified interactions between regions of the genome that encourage expression - promotors and enhancers, at different retinal development stages. They used machine learning to track how the organization of the genome was altered over time, and how easy it is to access certain regions so that the genes they contain can be expressed.

In this study, the scientists also observed a super-enhancer, which has a powerful regulatory effect on genes. It was active in a specific cell type at one particular stage. Importantly, super-enhancer function has been found to go awry in developmental brain cancer.

The super-enhancer influenced a gene called Vsx2, and when it was removed, the researchers found that one type of neuron, called bipolar neurons, was totally eliminated, although no other effects were seen. However, if the Vsx2 gene itself is deleted, there are many impacts on retinal development. This super-enhancer effect, therefore, seems to be very specific to bipolar neurons.

Data from the study and an instructional video can be found at St. Jude Cloud.

From the video above, learn more about a 3D map of the human genome that was generated several years ago and reported in Cell.

Sources: AAAS/Eurekalert! via St. Jude Research Hospital, Neuron

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JAN 22, 2020
Genetics & Genomics
JAN 22, 2020
A Way to Predict Which Microbes Can Cause Cancer
Researchers have created a technique that can identify bacteria and viruses that are linked to cancer....
JAN 22, 2020
Microbiology
JAN 22, 2020
New Drug Can Promote Resistance in the Flu Virus
A flu drug, while still safe and effective, encourages flu viruses to mutate, especially in children....
JAN 22, 2020
Genetics & Genomics
JAN 22, 2020
A New Threat to Christmas Trees is Discovered
Fraser firs are farmed to supply us with great-smelling Christmas trees that hold their needles, but they are also susceptible to molds....
JAN 22, 2020
Genetics & Genomics
JAN 22, 2020
Genetic Mutations Carried Only in Sperm May Affect a Child's Risk of Autism
Some genetic factors that contribute to ASD may involve mutations that are present only in a father's sperm....
JAN 22, 2020
Genetics & Genomics
JAN 22, 2020
How Dog Genomics Can Teach Us More About Human Health
It's been estimated that there are around 70 million pet dogs in the United States, with around 36 percent of households owning at least one dog....
JAN 22, 2020
Cardiology
JAN 22, 2020
Healthy Sleep May Offset Genetic Heart Disease Risk
People with a high genetic risk of heart disease or stroke may be able to offset that risk with healthy sleep patterns, according to new research. The rese...
Loading Comments...