Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover key step for regulating embryonic development

23.04.2010
New on-off switches: SUMO protein silences developmental genes, SNP2 snips SUMO to allow gene expression

Deleting a gene in mouse embryos caused cardiac defects and early death, leading researchers to identify a mechanism that turns developmental genes off and on as an embryo matures, a team led by a scientist at The University of Texas M. D. Anderson Cancer Center reported today in Molecular Cell.

"Our study focused on regulation of two genes that are critical to the healthy development of the heart, but many other genes are regulated in this way," said senior author Edward T.H. Yeh, M.D., professor and chair of M. D. Anderson's Department of Cardiology. "This novel pathway marks an advance in our understanding of how developmental genes are turned on and off."

All cells in an embryo contain the same DNA. Different genes are turned off and on in different cells at different times to form specific tissues and organs as the embryo develops. This gene regulation is accomplished by epigenetic processes that control gene expression without altering DNA. Instead, epigenetic processes attach chemical groups to genes or to histones, proteins that are intertwined with DNA to form chromosomes, to activate genes or to shut them down.

"Our findings provide a new window through which to look at epigenetic control," Yeh said, "and how epigenetics and development are unexpectedly tied together by the SUMO/SENP2 system."

The key actors are members of two tightly associated families of proteins that Yeh and colleagues discovered and continue to study. The first, Small Ubiquitin-related Modifier, or SUMO, attaches to other proteins to modify their function or physically move them within the cell (SUMOylation). The second, Sentrin/SUMO-specific protease 2, or SENP2, snips SUMO off of proteins (de-SUMOylation).

This line of research started when Yeh and colleagues knocked SENP2 out of mouse DNA and found that the embryos died at about day 10. Their hearts had smaller chambers and thinner walls. Through a series of experiments, the team worked backward from this observation to show:

A group of proteins called the polycomb repressive complex 1 (PRC1) that silences genes must first bind to a particular methylated address on a histone and,

A key component of the complex must be SUMOylated to make this connection, which results in

the silencing of Gata4 and Gata6, genes that are essential for cardiac development.

In early development, SENP2 works as a switch to turn on Gata4 and Gata6

"When SENP2 is turned on, it peels SUMO off of PRC1, which then falls off the histone, and when that happens, the lock is removed and genes are transcribed," Yeh said. Gata4 and Gata6 are free to properly develop the heart.

In short, SUMO helps the PRC1 complex repress genes, and SENP2 reverses this repression, allowing gene transcription and expression.

"By understanding how development unfolds, we can better control this process, which includes cell proliferation and organ development," Yeh said. "This will help us to better understand cancer.

"SUMO and SENP are important in cancer development, neurological diseases and heart development. Everything under the sun can be regulated by this system," Yeh said. "Here we've established a new role for SUMOylation, mediating the interaction between protein and protein methylation in epigenetic regulation."

Funding for this research was provided by from the National Natural Science Foundation of China, National Basic Research Program of China and grants from the U.S. National Cancer Institute. Yeh also is the McNair Scholar of the Texas Heart Institute/St. Luke's Episcopal Hospital.

Co-authors with Yeh are co-first author Yitao Qi, Ph.D., and Robert Schwartz, Ph.D., both of the Texas Heart Institute/St. Luke's Episcopal Hospital, and co-first author Xunlei Kang, M.D., Ph.D., Yong Zuo, Ph.D., Qi Wang, Yanqiong Zou and Jinke Cheng, D.V.M., all of the Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine in Shanghai.

About M. D. Anderson

The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 40 comprehensive cancer centers designated by the National Cancer Institute. For six of the past eight years, including 2009, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News & World Report.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

Further reports about: Cancer DNA PRC1 SENP2 Sumoylation cell death genetic processes mouse embryo neurological disease

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 >>>