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 Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Camera on NASA's Lunar Orbiter survived 2014 meteoroid hit

29.05.2017 | Physics and Astronomy

Strathclyde-led research develops world's highest gain high-power laser amplifier

29.05.2017 | Physics and Astronomy

A 3-D look at the 2015 El Niño

29.05.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>