Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly identified molecules contribute to normal silencing of most human genes

10.03.2003


Connections seen to X-linked mental retardation and some forms of leukemia



Most of the time, most of the estimated 35,000 genes in the human genome are silent, securely stored away in the tightly coiled structure of chromatin, which makes up chromosomes. Inside chromatin, the DNA is wound around small proteins called histones, making it unavailable to the cellular machinery that would otherwise read its coded genetic information. Specific cell and tissue types are characterized by the carefully controlled activation of selected sets of signature genes.

Now, a team of researchers at The Wistar Institute reports discovery of a family of molecular complexes involved in the repression of extensive sets of tissue-specific genes throughout the body. Additionally, one member of the family involved in repressing brain-specific genes in other types of tissues has been found to include a gene thought to be responsible for X-linked mental retardation when mutated. Other components of these complexes have been associated with certain forms of leukemia.


The new study appears in the current issue of the Journal of Biological Chemistry.

"One of the mysteries of gene expression is how different tissues in the body -heart, liver, brain - express the genes that are specific to them," says Ramin Shiekhattar, Ph.D., senior author on the report and an associate professor at The Wistar Institute. "What really controls this? For a long time, people have been looking for the factors that activate these genes, but what we and others are learning is that the critical mechanism used to regulate entire sets of genes is actually repression.

"In some ways, it’s like driving a car. You may not realize much driving relies on braking rather than acceleration. Without the brake, you can’t control the car."

The new findings may have relevance for understanding diseases characterized by uncontrolled or inappropriate gene activation and growth, with cancer perhaps the most significant of these.

The newly discovered molecular complexes share two core subunits and appear to operate as co-repressors with a number of tissue-specific repressor molecules to maintain the gene-silencing structure of chromatin.

One of the shared subunits is a type of enzyme, a so-called histone deacetylase, or HDAC, known to repress gene activation by modifying chromatin structure in specific ways. The second core subunit shared by these new complexes is called BHC110. This component, too, appears to be an enzyme, Shiekhattar says, although its specific activity remains to be determined.

Biochemical assays showed that BHC110 and the HDAC enzyme were both present in up to ten other unique complexes likely be involved in gene repression. Current experiments are aimed at learning more about the function of these two shared components of the complexes, and also at learning more about the components unique to each complex.

The equally contributing lead authors on the Journal of Biological Chemistry study are Mohamed-Ali Hakimi, Ph.D., and Yuanshu Dong, both at The Wistar Institute. William S. Lane at Harvard University collaborated on the study, as did Wistar professor David W. Speicher, Ph.D.


This research was supported by grants from the National Institutes of Health and the American Cancer 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.

News releases from The Wistar Institute are available to reporters by direct e-mail or fax upon request. They are also posted electronically to Wistar’s home page (http://www.wistar.upenn.edu), and to EurekAlert! (http://www.eurekalert.org), an Internet resource sponsored by the American Association for the Advancement of Science.


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

More articles from Life Sciences:

nachricht What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society

nachricht Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

What the world's tiniest 'monster truck' reveals

23.08.2017 | Life Sciences

Treating arthritis with algae

23.08.2017 | Life Sciences

Witnessing turbulent motion in the atmosphere of a distant star

23.08.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>