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 Cells communicate in a dynamic code
19.02.2018 | California Institute of Technology

nachricht Studying mitosis' structure to understand the inside of cancer cells
19.02.2018 | Biophysical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Contacting the molecular world through graphene nanoribbons

19.02.2018 | Materials Sciences

When Proteins Shake Hands

19.02.2018 | Materials Sciences

Cells communicate in a dynamic code

19.02.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>