Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study provides new insights into emerging theory of gene regulation

29.08.2003


With the full sequence of the human genome now in hand, scientists are turning renewed attention to the molecular processes that regulate the genes encoded by DNA. Estimates are that only a tenth of all genes are expressed at any given time. What controls when and where genes are activated?



Increasingly, researchers believe that the mechanisms that govern gene activity themselves resemble a complicated non-DNA code – an intricate pattern of activity among the molecules that package and control access to the DNA. They suspect that the coordinated interplay of a number of specific enzymes is required to turn on a particular gene.

Now, in a new study using the techniques of structural biology, investigators at The Wistar Institute have shown in detail how two enzymes work together to activate a specific gene by loosening, at that gene’s location, the compact coils of DNA and packaging proteins called chromatin. The findings bolster the emerging theory that something like a code is responsible for orchestrating genetic activity. A report on the research appears in the August issue of Molecular Cell, published August 28.


"This is the first time we’ve understood the precise mechanism of how two specific modifications to the DNA packaging proteins interact synergistically to promote the expression of a particular gene," says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and senior author on the study.

Most of the time, the great majority of genes are silenced, locked away within the packaging proteins of chromatin. For a given gene to be activated when needed, the chromatin must be opened at that gene’s location on the DNA, and that location only, to make the gene physically accessible for transcription. Histone proteins play a key role in this process.

Histones are relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strings of nucleosomes, then, form into chromatin, a substructure of chromosomes. When the DNA is tightly wrapped around the histones, the genes cannot be accessed and their expression is repressed. When the coils of DNA around the histones are loosened, the genes become available for expression, and it is the enzymatic activity governing this process in a specific case that Marmorstein’s laboratory was able to illuminate.

Working in yeast, Marmorstein and his colleagues showed that when a kinase enzyme adds a phosphoryl group to a histone molecule at a particular location, it helps a histone acetyltransferase enzyme to add an acetyl group at a second location on the same histone molecule. The acetylation of the histone then is thought to prompt a loosening of the DNA coils around the histone to permit transcription of the gene on that length of DNA.

"Five to ten years ago, most biologists thought that the proteins that package DNA served only to maintain physical order," Marmorstein notes. "It’s becoming clear, however, that these non-DNA elements of chromosomal structure dramatically influence gene expression. Proteins are coming on and off the DNA at specific times and locations to trigger the activation of genes."

The so-called "histone code" theory of gene regulation, advanced by C. David Allis, Ph.D., at the University of Virginia, and others, suggests that complex, interdependent modifications to the histones are responsible for controlling gene activity. The new data from the Wistar research team supports this view.

The two lead authors on the Molecular Cell study are Adrienne Clements, Ph.D., at Wistar, and Arienne N. Poux, at Wistar and the University of Pennsylvania. Wan-Sheng Lo, Ph.D., at Wistar, and Lorraine Pillus, at the University of San California, San Diego, are co-authors. Shelley L. Berger, Ph.D., the Hilary Koprowski Professor in the Gene Expression and Regulation Program at Wistar, was a collaborator and co-author on the study.

An earlier study by Berger and Wistar associate professor Ramin Shiekhattar, Ph.D., published in the August 10, 2001, issue of Science, reported the link between the two chromatin-modifying events, but details concerning the mechanism of action remained to be determined in the current research project.

Primary funding for the research was provided by the National Institutes of Health. Additional support came from the Commonwealth of Pennsylvania and the Leukemia & Lymphoma Society.

The Wistar Institute is an independent nonprofit biomedical research institution dedicated to discovering the causes and cures for major diseases, including cancer, cardiovascular disease, autoimmune disorders, and infectious diseases. Founded in 1892 as the first institution of its kind in the nation, The Wistar Institute today is a National Cancer Institute-designated Cancer Center – one of only eight focused on basic research. Discoveries at Wistar have led to the development of vaccines for such diseases as rabies and rubella, the identification of genes associated with breast, lung, and prostate cancer, and the development of monoclonal antibodies and other significant research technologies and tools.

Franklin Hoke | EurekAlert!
Further information:
http://www.wistar.upenn.edu/

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>