Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study pinpoints regulator of imprinted gene expression

10.03.2003


Fndings in mice hold implications for human disorders



New research at the University of North Carolina at Chapel Hill offers an important contribution to a new wave of thinking in genetics: the idea that not all human disease states are due to alterations in DNA sequence.

A growing body of research on these "epigenetic" changes are leading geneticists to rethink the conventional view that all human disease is fundamentally tied to DNA sequence variation (changes in the actual sequence of the DNA nucleic acid code of A’s, C’s, G’s and T’s within any given gene).


The DNA within human cells contains the information for roughly 35,000 different proteins that carry out the body’s functions. But not all of these genes are active all of the time. Like switches, epigenetic modifications to proteins surrounding the DNA regulate a given gene’s activity, such that only those that are required in a particular cell are active (switched on). These changes constitute a "memory" of gene activity that can be passed on each time a cell divides.

If these epigenetic modifications do not occur properly, the result can cause some genes to become switched on or off incorrectly, thereby having profound biological consequences. Incorrect epigenetic modifications have been implicated in many human disorders including several types of cancer, birth defects and mental retardation.

"These expression changes are heritable and are not related to sequence changes in the gene that is directly affected", said Dr. Terry Magnuson, Kenan professor of genetics and director of the Carolina Center for Genome Sciences. "Sequencing the human genome will not necessarily lead one to discover why these genes are expressed abnormally."

For example, there is a recent awareness among scientists of a new type of health threat posed by environmental chemicals that can disrupt endocrine signals during critical periods of development through epigenetic alterations. Additionally, researchers studying Rett syndrome (a rare neurological disease) have found that the mutated gene exerts its effect by influencing epigenetic modifications elsewhere in the genome.

A new study, published online in Nature Genetics on Monday (March 10) makes a case for epigenetics by identifying a gene that may be critical for proper epigenetic changes. The new study shows for the first time that the gene called "Eed" is required for the proper epigenetic regulation of a subset of genes that normally show parent of origin expression, known as genome imprinting. Genome imprinting is a phenomenon in which only one copy of specific genes are active, or switched on. Which copy is active depends upon whether they are inherited from the mother or the father.

When Eed is mutated or its function impaired, loss of imprinting can occur - both the maternal and paternal copy become active.

The new work builds on previous research by Magnuson’s group. In that work, Eed was shown to maintain the molecular brakes on the paternal X chromosome, keeping many of its genes inactive, thus preserving female embryo survival. The study team created female mouse embryos that lacked a copy of Eed. As a result, the paternal X chromosome was shut down only temporarily and then came back on with subsequent problems in placental formation.

"Basically, Eed forms a complex of proteins and alters those chromosomal proteins that affect the configuration of the chromosome so as to allow or not allow expression. If this gene, Eed, isn’t functioning properly, the imprint is lost resulting in incorrect activity of specific genes," Magnuson said.

"We learned from the Human Genome Project that in a complex organism like humans, the 35,000 genes must act in concert with one another in many different combinations at many different times," he added. "So understanding how genes are regulated in terms of their expression, how they are turned on and off, and if they are off how they are maintained in that ’off’ state, becomes critical. This study opens up new possibilities for looking into mechanisms responsible for epigenetic alterations in human disorders."

Along with Magnuson, study co-authors are Jesse Mager and Nathan Montgomery, graduate students in the Curriculum in Genetics and Molecular Biology; and Dr. Fernando Pardo-Manuel de Villena, assistant professor of genetics and member of the UNC Lineberger Comprehensive Cancer Center.


The research was funded by the National Institute of Child Health and Human Development, part of the National Institutes of Health.

Note: Media can obtain access to the on-line paper through Katie Goldrick, Nature Publications, at (202) 737-2355. Contact Magnuson at (919) 843-6475 or terry_magnuson@med.unc.edu

School of Medicine contact: Leslie 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 Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>