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 What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>