Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeting transcription: New insights into turning genes on

12.09.2003


The 35,000 or so genes within a human cell are something like players on a sports team: If their activity isn’t controlled and coordinated, the result can be disastrous.



So just as coaches tell individual players when to scramble onto the field and when to stay on the bench, molecules called transcription factors prompt particular genes to be active or stay quiet. Transcription factors occur naturally in cells, but researchers have been working to develop artificial transcription factors (ATFs) that can be tailored to regulate particular genes or sets of genes. These molecules can help scientists probe transcription, the first step in the process through which instructions coded in genes are used to produce proteins. And because errors in transcription are linked to diseases ranging from diabetes to cancer, ATFs eventually might also be used to correct those mistakes.

Using a new approach to developing ATFs, University of Michigan assistant professor of chemistry Anna Mapp and coworkers have gained important insights into the workings of gene-activating transcription factors. They recently discovered that the gene-activating power of a transcription factor likely depends on where the factor binds to the cell’s transcriptional machinery, as well as on how tightly it binds. Previously, researchers had thought that binding affinity (tightness) was the main determinant of a gene activator’s potency. Mapp presented the group’s results at the annual meeting of the American Chemical Society in New York today (Sept. 8).


Natural transcription factors typically have two essential parts or modules: a DNA-binding module that homes in on the specific gene to be regulated and a regulatory module that attaches itself to the cell’s transcriptional machinery through a key protein-to-protein interaction and activates or represses the gene.

"When we started thinking about making artificial transcription factors, we knew we needed to find molecules that had that same binding interaction," Mapp said. Other researchers have created ATFs by shuffling combinations of DNA-binding modules and regulatory modules, typically using regulatory modules that are derived from or resemble natural ones. Mapp’s group took a different approach in hopes of creating smaller ATFs that might be easier to introduce into cells and less likely to be degraded or trigger an immune response---features that would be critical if ATFs are ever to be used in treating disease.

The Michigan team first isolated and purified a protein from the cell’s transcriptional machinery; then they screened large groups of synthetic peptides (short chains of amino acids) for their ability to bind to the protein.

"From that, we got molecules that seem to bind to several different surfaces of the protein," Mapp said, "and we could use that binding interaction to activate transcription in some cases. So we were able to see for the first time that differences in binding site location may actually affect regulator function."

The artificial activators are much smaller than most known natural activators. Using the same kind of screening approach, the researchers now plan to search for small organic molecules that are structurally similar to their protein-binding peptides and to combine those molecules with small DNA-binding modules already developed by other researchers, with the goal of creating new ATFs.

Nancy Ross-Flanigan | EurekAlert!
Further information:
http://www.umich.edu/~newsinfo
http://www.umich.edu/~michchem/faculty/mapp
http://www.umich.edu/news/paper0903.html

More articles from Life Sciences:

nachricht Research on TGN1412 – Fc:Fcγ receptor interaction: Strong binding does not mean strong effect
23.04.2019 | Paul-Ehrlich-Institut - Bundesinstitut für Impfstoffe und biomedizinische Arzneimittel

nachricht Simple and Fast Method for Radiolabelling Antibodies against Breast Cancer
23.04.2019 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

New automated biological-sample analysis systems to accelerate disease detection

18.04.2019 | Life Sciences

Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

18.04.2019 | Physics and Astronomy

New eDNA technology used to quickly assess coral reefs

18.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>