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Stanford scientists identify protein that keeps stem cells poised for action
Date:12/24/2009

c stem cells than in non-stem cells.

Jarid2 had been previously identified as a protein important during development. But its role in embryonic stem cells hadn't yet been addressed. The Stanford researchers found that together PRC2 and Jarid2 occupied specific stretches of histone-bound DNA in both mouse and human embryonic stem cells. When they reduced the amount of Jarid2 in the cells, PRC2 was less able to bind the DNA and the cell began to churn out the proteins before they were needed confirming Jarid2's importance in stem cell differentiation.

Surprisingly, though, the degree of modifications on the histones remained about the same, even though less PRC2 was bound to the DNA. This suggested that when PRC2 is bound to Jarid2, it puts fewer "don't open" tags on the histones.

"This was a crucial finding," said Wysocka, "because it shows that Jarid2 both recruits PRC2 to the DNA and modulates its ability to modify the histones." It also suggests that the Jarid2/PRC2 complex inhibits gene expression in other, as-yet-unidentified ways. Such fine-tuning of PRC2 activity, the researchers believe, allows the cell to carefully manage its degree of readiness for the subsequent unwrapping and expression of genes involved in differentiation of the embryonic stem cells into more specialized cells.

The researchers confirmed their findings in frog embryos, which are more easily studied at early stages of differentiation than are mouse embryos, by depleting Jarid2 expression. They found that embryos missing Jarid2 were unable to complete a critically important developmental step called gastrulation.

"It was just as we would have predicted," said Wysocka. "Without Jarid2, which keeps the genes silent yet poised for activation, the embryos stop developing." The researchers now plan to further investigate the mechanism by which Jarid2 summons PRC2 to differentiation-specific genes in the stem cells, and how it affects gene expression.
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Contact: Krista Conger
kristac@stanford.edu
650-725-5371
Stanford University Medical Center
Source:Eurekalert

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