Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

U.VA. scientists find new piece of gene expression puzzle

28.06.2002


Scientists at the University of Virginia Health System have identified another step in the mysterious process of gene regulation -- what turns genes on or off, making them cause or suppress disease and other physical developments in humans. As reported in this week’s issue of the scientific journal Nature, a chemical group called ubiquitin has been shown to lie upstream of a switch that seems to control whether a gene is on or off. "Ubiquitin was first discovered on histones long ago, but before this study, we really did not know what it was doing in chromatin," said lead author and investigator Zu-Wen Sun, senior post-doctoral fellow in the Department of Biochemistry and Molecular Genetics at U.Va. Ubiquitin is one of manydistinct kinds of chemical "flags" that are known to be present on histone proteins.

Histones are protein building blocks around which the DNA is coiled much like a Slinky toy. Together, they form a structure called chromatin, where additional levels of gene regulation occur outside the DNA itself. One mechanism for regulating gene expression in the form of chromatin is through the addition or removal of chemical groups that are attached to the histone proteins. These histone proteins are nearly identical in most complex living organisms, from humans to yeast, which was used as a model in this study. They are highly decorated with different kinds of chemical groups including methyl- and acetyl- groups. Distinct patterns of these marks may operate together to form a ’histone code’ that, in turn, precedes and influences gene activities within the chromatin, according to studies published last year by C. David Allis, Byrd Professor of Biochemistry and Molecular Genetics at U.Va., who is co-author of the new study.

The four major types of histones each have a long "tail" which "wags" outside the surface of the chromatin fiber. Last year’s studies examined lysines at the fourth (K4) and ninth (K9) positions on the tail of one of the histones, H3, and revealed that when a chemical methyl group is added to these two positions, it turns genes on or off, acting much like a master control switch according to a histone code.



The new study found an unexpected mechanism that dictates whether methylation occurs at the K4 position of H3. It showed that another chemical group called ubiquitin, which is attached on the tail of a completely different histone, H2B, affected methylation of lysine at this K4 position on the H3 tail. This phenomenon, referred to as "trans-tail" regulation of the histone’s chemical changes, was unexpected, Sun said, because all other related chemical reactions previously identified, such as methylation of K4 and K9 lysines, occurred in relatively close proximity on the same histone tail.

"It is the first time that the modification on one histone’s tail has been seen to affect what occurs on another histone tail," he said. "And, in addition, we now understand better how the ubiquitin and the enzyme responsible for adding it to the histone H2B in the first place is linked to gene regulation."

Sun and Allis said that defects in the ubiquitin pathway in mice already have been generally connected to male infertility. It is possible that the problem could be traced from defects in the addition of the ubiquitin group in chromatin, to defects in the addition of the methyl group, and to subsequent changes in gene expression, which then disturbs proper cell differentiation.

"It means we have to start looking at how the whole group of these histone proteins functions together as a unit, as well as individually," Allis said. "If the ubiquitin chemical flag seems to govern methylation of lysine at K4, but not elsewhere, there is a selectivity going on, and it’s remarkably more complicated than we thought. When we reported on the methylation of lysine at K4 and K9 last summer, we had no clue it was being regulated by something else as described in our new study. So we would like to find out what is it about ubiquitin that causes such a dramatic influence on histone methylation.

"It’s a new chain reaction for chromatin," he said. "It is a major new finding in this field with a very old histone modification."

The study was funded by the National Institutes of Health and the U.Va. Cancer Center.

Catherine Wolz | EurekAlert!
Further information:
http://www.nih.gov/
http://hsc.virginia.edu/medcntr/cancer/

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>