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Scientists discover key step for regulating embryonic development
Date:4/22/2010

HOUSTON 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 expe
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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