Nav: Home

Study sheds more light on genes' 'on/off' switches

February 26, 2019

It takes just 2 percent of the human genome to code for all of the proteins that make cellular functions -- from producing energy to repairing tissues -- possible.

So what does the other 98 percent do?

A large portion of this so-called noncoding DNA controls the expression of genes, switching them on and off. This regulation is essential because every cell has the same DNA.

In other words, the only thing that makes a muscle cell different from a brain cell is which genes are activated.

It's why University of Michigan scientists are using sophisticated computational methods to investigate how genetic variation in noncoding DNA can increase a person's susceptibility to certain diseases, such as diabetes and cancer.

In a new paper in the journal Genetics, they compare five types of regulatory regions that have been identified in the past few years in an effort to figure out how the regions behave in different types of cells.

"When people try to look at how gene regulation occurs, they look at different epigenomic information using sequencing, trying to understand molecular profiles," says lead author Arushi Varshney, a Ph.D. candidate in human genetics.

Epigenomics refers to changes in the organization of genes caused by factors other than the DNA sequence.

For example, researchers have recently discovered that genetic variants -- the slight variations in DNA that make us unique -- that are associated with diseases tend to lie in areas of the genome that act as gene regulatory elements called enhancers and promoters.

Enhancers boost the rate of transcription of a gene, much like the accelerator in a car, and promoters initiate transcription of a gene, like a car's ignition.

"There were a number of papers coming out describing different classes of gene regulatory elements, and it was not clear how they are related," explains Stephen Parker, Ph.D., assistant professor of computational medicine and bioinformatics and of human genetics.

"Our paper was the first to really compare them," Parker says. "One of the things that came out is that they're all different and act differently in different cell types."

However, the U-M team also discovered that genetic variants in the more cell type-specific enhancers have relatively small effects on their target genes. This could spell trouble for scientists who are comparing thousands of people's genomes to try to locate genetic variation associated with disease traits.

The U-M authors suggest that these genes are so important for a cell's function that their transcription is tightly regulated under normal conditions.

"What it means is we're going to need really large sample sizes to see effects," Parker says.

Another unexpected finding may eventually explain how genetic variation in regulatory elements makes disease more likely.

Varshney, Parker and their colleagues suggest that enhancers and promoters that are cell-specific -- meaning they have bigger effects in certain types of cells -- could make it easier for transcription to occur under certain environmental conditions.

They appear to do this by making the cell's chromatin, the dense protein molecules that the DNA wraps around inside the nucleus of a cell, more accessible.

As a next step in this research, "we think one should look at gene expression of cells under specific conditions," Varshney says. "For example, if you're trying to look at type 2 diabetes, maybe look at cells under high glucose conditions, then look at the gene expression and how genetic variants affect gene expression.

"Then, maybe you would be better able to explain how this genetic variant predisposes you to get a disease."
-end-


Michigan Medicine - University of Michigan

Related Dna Articles:

Penn State DNA ladders: Inexpensive molecular rulers for DNA research
New license-free tools will allow researchers to estimate the size of DNA fragments for a fraction of the cost of currently available methods.
It is easier for a DNA knot...
How can long DNA filaments, which have convoluted and highly knotted structure, manage to pass through the tiny pores of biological systems?
How do metals interact with DNA?
Since a couple of decades, metal-containing drugs have been successfully used to fight against certain types of cancer.
Electrons use DNA like a wire for signaling DNA replication
A Caltech-led study has shown that the electrical wire-like behavior of DNA is involved in the molecule's replication.
Switched-on DNA
DNA, the stuff of life, may very well also pack quite the jolt for engineers trying to advance the development of tiny, low-cost electronic devices.
Researchers are first to see DNA 'blink'
Northwestern University biomedical engineers have developed imaging technology that is the first to see DNA 'blink,' or fluoresce.
Finding our way around DNA
A Salk team developed a tool that maps functional areas of the genome to better understand disease.
A 'strand' of DNA as never before
In a carefully designed polymer, researchers at the Institute of Physical Chemistry of the Polish Academy of Sciences have imprinted a sequence of a single strand of DNA.
Doubling down on DNA
The African clawed frog X. laevis genome contains two full sets of chromosomes from two extinct ancestors.
'Poring over' DNA
Church's team at Harvard's Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School developed a new electronic DNA sequencing platform based on biologically engineered nanopores that could help overcome present limitations.

Related Dna Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Changing The World
What does it take to change the world for the better? This hour, TED speakers explore ideas on activism—what motivates it, why it matters, and how each of us can make a difference. Guests include civil rights activist Ruby Sales, labor leader and civil rights activist Dolores Huerta, author Jeremy Heimans, "craftivist" Sarah Corbett, and designer and futurist Angela Oguntala.
Now Playing: Science for the People

#521 The Curious Life of Krill
Krill may be one of the most abundant forms of life on our planet... but it turns out we don't know that much about them. For a create that underpins a massive ocean ecosystem and lives in our oceans in massive numbers, they're surprisingly difficult to study. We sit down and shine some light on these underappreciated crustaceans with Stephen Nicol, Adjunct Professor at the University of Tasmania, Scientific Advisor to the Association of Responsible Krill Harvesting Companies, and author of the book "The Curious Life of Krill: A Conservation Story from the Bottom of the World".