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 Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>