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 Water world
20.11.2017 | Washington University in St. Louis

nachricht Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Antarctic landscape insights keep ice loss forecasts on the radar

20.11.2017 | Earth Sciences

Filling the gap: High-latitude volcanic eruptions also have global impact

20.11.2017 | Earth Sciences

Water world

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>