Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Insight into Control of Parental Gene Expression in Eggs

09.01.2004


Researchers have identified a crucial step in a genetic process required for the development of viable eggs. The process, known as imprinting, distinguishes the paternally-inherited and the maternally-inherited copies of a number of developmentally important genes.



The majority of mammalian genes are present in two copies, both of which are equally expressed and regulated. A small number of mammalian genes, however, are subject to special regulation by a process called gene imprinting. The imprint is a chemical mark, such as methylation, attached to genes during egg or sperm development. Imprinting physically marks genes in such a way that the parental origin of the two copies can be distinguished so that one parent’s copy is turned on while the other is silenced. Imprinted genes are the likely reason that maternal and paternal contributions are necessary for normal mammalian development.

Exploring the mechanisms underlying gene imprinting may provide insight into so-called epigenetic control of gene expression, in which the cellular machinery governs the expression of genes in the cell. The function of that machinery, which makes modifications to the genome, remains among the major mysteries in biology.


Howard Hughes Medical Institute investigator Marisa S. Bartolomei, Andrew Fedoriw, Paula Stein, Petr Svoboda and Richard Schultz at the University of Pennsylvania published their findings in the January 9, 2004, issue of the journal Science.

The researchers sought to pinpoint the regulatory role of a protein known as CTCF, which is believed to attach to a control region near imprinted genes. By binding to this region, called the differentially methylated domain, CTCF blocks the site from the attachment of methyl groups to the DNA — chemical modifications that the cell’s epigenetic machinery uses to silence genes.

Bartolomei and her colleagues focused on the role of CTCF in protecting a gene called H19, whose paternal version is silenced in the developing embryo while the maternal version remains active.

To determine whether CTCF might be protecting the maternal copy of H19 from DNA methylation, the researchers used a technique called RNA interference, in which they genetically engineered mouse eggs to produce RNA molecules that can interfere with a particular messenger RNA (mRNA). In this case, the mRNA for the CTCF protein was targeted. This technique in effect degrades the target mRNA, thereby reducing the level of the protein for which it codes.

The researchers generated and studied a series of mouse eggs that exhibited different levels of RNA interference, resulting in different amounts of the CTCF protein. They found that the lower the level of CTCF in the developing eggs, the higher the methylation of the regulatory domain for H19. They also observed that female mice that developed from the eggs with the lowest levels of CTCF protein showed profoundly reduced fertility.

"While this is certainly an indirect experiment — in that we depleted the CTCF protein and saw that DNA methylation was acquired — it is nevertheless persuasive evidence of the interaction of CTCF with the differentially methylated domain of H19," said Bartolomei. "It’s a finding that makes good intuitive sense.

"What’s important about this experiment is that it demonstrates that CTCF appears to be actively protecting the H19 gene," she said. "And importantly, we have demonstrated the utility of this gradation RNA-interference technique that we believe will be invaluable for studying the functions of proteins whose complete ablation by the usual knockout techniques would be lethal."

More broadly, said Bartolomei, such studies investigating the regulation of imprinting are likely to yield new insight into the machinery underlying the epigenetic control of gene expression. "Our findings suggest that there are critical sequences at imprinted genes that are recognized and can be marked by or protected from DNA methylation," she said. "These sequences that regulate imprinted genes are not straightforward, however, but are more complicated ones that we are not able to predict by sequence analysis alone."

An important future direction for the research, she said, is to identify more genes similar to H19 that are subject to CTCF-dependent imprinting control and to use RNA interference and other techniques to explore the nature of that control.

"Until the availability of this technology, it has been an essentially intractable problem to look at imprinting establishment in the early embryo," said Bartolomei. "But using these newly developed technologies we can now test candidate molecules that might be critical for conferring imprinting.

"We want to identify other paternally-methylated and maternally-unmethylated regions to see if CTCF might be a general protector against methylation," she said. "Further, we’ve shown that these embryos produce mice with dramatically reduced litter sizes, and we’d like to understand the nature of the defects as a way to understand the role of CTCF."

Jim Keeley | HHMI
Further information:
http://www.hhmi.org/news/bartolomei.html

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

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

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>