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Study finds protein that plays key role in early embryonic development
Date:5/12/2010

anscription factorwhich regulates other genes. In 2005, Stoller and Epstein found that within this protein, also called TBX1, a particular domain was crucial and played a key role in chromosome 22q.11 deletion syndrome.

The current study, said Stoller, aimed to discover proteins that interact with the Tbx1 protein and to identify some of the biological events that give rise to chromosome 22q.11 deletion syndrome. The study team identified the protein Ash2l as an important partner of Tbx1. "The two proteins act together to influence other genes that may impair biological systems affected in the deletion syndrome," said Stoller. "Ash2l is important in epigeneticschanges in gene activity that do not involve alterations to the genetic code spelled out in DNA." In epigenetic processes, chemical groups attached either to DNA, or to DNA-associated proteins called histones, switch gene activity on or off.

Many other steps resulting from this protein interaction have yet to be discovered, to determine how these molecular events cause specific effects, such as cleft palate or abnormalities in the thymus gland that occur in chromosome 22q.11 deletion syndrome. Said Stoller, "As with much research in basic science, discovering gene pathways and biological mechanisms may lay the foundation for future development of drugs or other therapies to act on these pathways, but such clinical applications are still in the future."

Another finding in the current study does not directly affect patients with the deletion syndrome, but shows that the Ash2l protein is absolutely essential to normal development. Mice that were bred to lack the gene for Ash2l produced embryos that, without exception, died very early in gestation. "The fact that this protein is necessary to early embryonic survival suggests that Ash2l regulates many genes during the early stages of development," said Stoller.


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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

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