Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UNC researchers identify protein crucial to gene silencing

03.09.2003


A cellular protein identified by scientists at the University of North Carolina at Chapel Hill may be the crucial molecular element for gene silencing.



The research findings, published Aug. 29 in the science journal Molecular Cell, add important knowledge to the understanding of epigenetic signals. These chemical signals affect the modulation of gene expression - activation or repression - throughout the genome.

Studies at UNC and elsewhere have shown that epigenetic phenomena underpin the shutting down of one copy of the X chromosome occurring in female mammals, and parental "imprinting" - in which a gene’s activity depends on whether it’s inherited from the mother or father. During development, the expression of whole sets of genes must be repressed, or silenced, after their proteins set the body pattern.


One such epigenetic event is histone methylation, the addition of one or more methyl groups to lysine, one of the amino acids that make up the "tail" domain of histone proteins. Within the cell nucleus, spiraling strands of DNA are wrapped tightly around four core histone proteins and then fold to form a densely packed structure called chromatin. This complex of nucleic acids and proteins packages DNA into higher order structures, ultimately forming a chromosome.

The chemical modification of histone tails can alter chromatin structure, loosening or tightening it, which in turn influences the expression of adjacent genes. In the journal article, a study team led by Dr. Yi Zhang, assistant professor of biochemistry and biophysics in UNC’s School of Medicine and a member of UNC’s Lineberger Comprehensive Cancer Center, reported having identified for the first time a protein that directly regulates lysine methylation on the core histone protein, H3, in a way that represses gene activity.

"We have found the first molecule, the first gene product, that can regulate methylation," Zhang said.

In earlier research, Zhang identified a catalytic subunit associated with lysine methylation. This is the murine (mouse) enzyme ESET and its human homologue SETDB1. However, subsequent studies showed that such methylation might not be enough by itself to trigger gene silencing.

The newly discovered murine regulatory protein is called "mAM." Its human equivalent, or homologue, is "hAM." Stimulated by this protein, the state of methylation of lysine-9 on H3 that’s produced by the enzymatic subunit is made more complex - moving from dimethylation, the addition of two methyl groups, to trimethylation, the addition of three. In this new state, lysine-9 methylation becomes the signal for gene repression.

While the catalytic subunit alone can methylate a particular lysine residue on H3, in this case lysine-9, gene silencing occurs only when the lysine is methylated to the trimethyl state, Zhang said.

"The catalytic subunit by itself can have enzymatic activity, but not enough potency to repress gene expression," Zhang said. "Now we have demonstrated both in vitro and in vivo that gene repression is dependent on trimethylation." Zhang and his team are studying the biological significance of their discovery. "We have some indications that it’s important for apoptosis, programmed cell death. We’re also studying chromatin epigenetics with a view toward determining if they play a role in the ability of stem cells to commit to a specific lineage."

Along with Zhang, UNC co-authors of the report include Drs. Hengbin Wang and Li Xia and doctoral student Ru Cao. Other co-authors are Woojin An and Robert G. Roeder of Rockefeller University; Hediye Erdjument-Bromage and Paul Tempst of Memorial Sloan-Kettering Cancer Center in New York; and Bruno Chatton of CNRS-INSERM, in Strasbourg, France.


The research was supported by a grant from the National Institute of General Medicine, a component of the National Institutes of Health.

Note: Contact Zhang at (919) 843-8225 or yi_zhang@med.unc.edu.
School of Medicine contact: Les Lang, (919) 843-9687 or llang@med.unc.edu

By LESLIE H. LANG
UNC School of Medicine

Leslie Lang | EurekAlert!
Further information:
http://www.med.unc.edu/

More articles from Life Sciences:

nachricht Chains of nanogold – forged with atomic precision
23.09.2016 | Suomen Akatemia (Academy of Finland)

nachricht Self-assembled nanostructures hit their target
23.09.2016 | King Abdullah University of Science and Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Chains of nanogold – forged with atomic precision

23.09.2016 | Life Sciences

New leukemia treatment offers hope

23.09.2016 | Health and Medicine

Self-assembled nanostructures hit their target

23.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>