KANSAS CITY, MOUnlike less versatile muscle or nerve cells, embryonic stem cells are by definition equipped to assume any cellular role. Scientists call this flexibility "pluripotency," meaning that as an organism develops, stem cells must be ready at a moment's notice to activate highly diverse gene expression programs used to turn them into blood, brain, or kidney cells.
Scientists from the lab of Stowers Investigator Ali Shilatifard, Ph.D., report in the December 27, 2012 online issue of Cell that one way cells stay so plastic is by stationing a protein called Ell3 at stretches of DNA known as "enhancers" required to activate a neighboring gene. Their findings suggest that Ell3 parked at the enhancer of a developmentally regulated gene, even one that is silent, primes it for future expression. This finding is significant as many of these same genes are abnormally switched on in cancer.
"We now know that some enhancer misregulation is involved in the pathogenesis of solid and hematological malignances," says Shilatifard. "But a problem in the field has been how to identify inactive or poised enhancer elements. Our discovery that Ell3 interacts with enhancers in ES cells gives us a hand-hold to identify and to study them."
In 2000, Shilatifard identified Ell3 as the third member of the Ell (for "Eleven-nineteen lysine-rich leukemia gene") family of elongation factors, proteins that increase the rate at which genes are expressed. "At the time, we didn't think much of Ell3 because it was highly expressed in testes," says Shilatifard, noting that then people thought that sperm were merely vessels used to carry paternal DNA to an egg and that associated factors would have little relevance to the regulation of future gene expression in the resulting embryo.
But a few years back, a curious Open University graduate student working in the Shilatifard lab, Chengqi Lin, started exploring a potential function for the neglec
|Contact: Gina Kirchweger|
Stowers Institute for Medical Research