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Stowers study hints that stem cells prepare for maturity much earlier than anticipated
Date:12/27/2012

ted gene by initiating a global search for regions occupied by Ell3 in the genome of mouse embryonic stem cells. His search in collaboration with a bioinformatician in the Shilatifard lab, Alexander S. Garruss, revealed that Ell3 sits on more than 5,000 enhancers, including many that regulate genes governing stem cell maturation into spinal cord, kidney, and blood cells.

"What was interesting was that Ell3 marked enhancers that are active and inactive, as well as enhancers that are known as "poised," says Lin, referring to a transition state from inactive to active. "That indicated that Ell3's major function might be to prime activation of genes that are just about to be expressed during development."

The fact that silent genes can be "primed" for expression was no surprise: researchers knew that the enzymatic machine that copies DNA into the RNA blueprint for proteinsa protein called Pol IIoften pauses at the start of a gene, presumably revving its engine in preparation to jump across the genetic start gate in response to a developmental signal. However, Shilatifard and colleagues showed several years ago that paused Pol II is not a prerequisite for rapid transcriptional induction.

The surprise came when researchers used a molecular trick to deplete mouse ES cells of Ell3 and then did a "genomic" survey. They found that paused Pol II vanished from the start sites of many genes in Ell3-deficient cells. This means that not only does Ell3 preferentially mark stem enhancers, but also that its presence there is necessary to keep an idling Pol II ready for action.

Most of the current study defines how, when the developmental time is right, enhancer-bound Ell3 cooperates with components of a big-boss elongation factor called the Super Elongation Complex to release Pol II from the start gate, allowing the expression of genes required for stem cell differentiation. Critical among those findings is their observation that mouse stem cell
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Contact: Gina Kirchweger
gxk@stowers.org
816-806-1036
Stowers Institute for Medical Research
Source:Eurekalert  

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