Nav: Home

How transcription factors explore the genome

January 30, 2019

Transcription factors (TFs) are proteins that regulate the transcription of genes, which is the first step in making a protein. The way TFs work is by searching the entire genome and binding to specific regions that regulate genes, turning them "on" or "off". TFs are known to not only bind to specific sequences of DNA, but also to non-specifically bind to any stretch of DNA.

This non-specific association can drastically increase the ability of TFs to find their specific target sites by allowing them to slide along DNA. However, we do not understand how the more than 1,500 human TFs vary in their efficiency to scan the massive genome, locate and bind specific sites.

Now, the lab of David Suter at EPFL's Institute of Bioengineering has found a way to predict the efficiency with which different TFs scan the genome in living cells. The scientists studied 501 TFs in the mouse by looking at how they bind to "mitotic" chromosomes, a property that has been linked to the ability of TFs to associate with DNA in a non-specific manner.

Using photobleaching experiments and single molecule imaging, the scientists found that TFs movements in the nucleus and the efficiency at which they find their binding sites can be predicted by mitotic chromosome binding.

By combining these experiments with the TF mapping in the whole genome, they found that different TFs vary by three orders of magnitude in their ability to find their sites. Thus, TF with strong non-specific DNA binding properties associate with mitotic chromosomes, move slowly in the nucleus and are particularly efficient at finding the specific sequences they need to bind to regulate gene expression.

"Transcription factors differ largely in their ability to scan the genome to find their specific binding sites, and these differences can be predicted by simply looking at how much they bind to mitotic chromosomes," says David Suter. "Transcription factors that are the most efficient in searching the genome could be able to drive broad changes in gene expression patterns even when expressed at low concentrations, and can therefore be particularly important for cell fate decision processes."
-end-
Other contributors

Ulm University

Reference

Mahé Raccaud, Elias T. Friman, Andrea B. Alber, Harsha Agarwal, Cédric Deluz, Timo Kuhn, J. Christof M. Gebhardt, David M. Suter. Mitotic chromosome binding predicts transcription factor properties in interphase. Nature Communications 30 January 2019. DOI: 10.1038/s41467-019-08417-5.

Ecole Polytechnique Fédérale de Lausanne

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".