Friday, 28 December 2012

Stowers researchers announce new interesting findings about embryonic stem cells

The main difference between embryonic stem cells (ES cells) and adult stem cells is their degree of potency.  ES cells have a higher degree of potency and are characterized as pluripotent, meaning that they can develop into almost all kind of different types of cells. Researchers from the Stower Institute published today on the online magazine Cell, their most recent findings on Ell3 that explain some of the mechanisms employed by embryonic stem cells.

The Ell3 protein is stationed at stretchers of DNA called enhancers. It is the third member of the Ell family of elongation factors which are proteins that increase the rate of genes expressed. According to the researchers the presence of Ell3 in enhancers, plays a significant role on whether or not a gene will be expressed, even in the case of silent genes. They believe their discovery is very important, as many times these genes are abnormally activated during cancer development. Ali Shilatifard, Ph.D., said

We now know that some enhancer misregulation is involved in the pathogenesis of solid and hematological malignances,” and added, “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.” 

Ell3 was first identified by Shilatifard in 2000. However he didn't thought much about his discovery

 “At the time, we didn’t think much of Ell3 because it was highly expressed in testes,” , Shilatifard said, mentioning the fact that back then, people believed that the sperm's only role was simply to transfer DNA from the male to the female's egg, thus any associated factors would have little, if any, importance to the regulation of future gene expression in the embryo.

It wasn't but a few years later, that the importance of Ell3 was discovered by a graduate student ,Chengqi Lin , working in Shilatifard's lab. Lin collaborated with bioinformatician Alexander S. Garruss and searched for a potential function of Ell3, looking for regions in the genome of mouse ES cells that might be occupied by Ell3. Their search showed that Ell3  was stationed in more that 5,000 enhancers. Many of these enhancers were responsible for genes accountable for stem cells developing into spinal, kidney, blood cells and other. 

“What was interesting was that Ell3 marked enhancers that are active and inactive, as well as enhancers that are known as “poised,” said Lin, about the progression from the state of inactive to active, adding “That indicated that Ell3’s major function might be to prime activation of genes that are just about to be expressed during development.”

Picture of RNA polymerase II
RNA polymerase II

During their experiments the team was surprised when it depleted mouse ES cells of all Ell3. During their “genomic” survey, they found that RNA polymerase II had vanished as well. This means that not only Ell3 marks stem enhancers, but its presence also acts a prerequisete  to keep an idling RNA polymerase II ready for action.

In summary the key findings of their research are the following:
  • Highlights Ell3 is preferentially found at active, poised, and inactive enhancers in embryonic stem cells 
  • Promoter-proximal RNA polymerase II occupancy at key developmental genes requires Ell3 
  • Cohesin functions in Ell3-associated enhancer-promoter communication 
  • Recruitment of P-TEFb within SEC during differentiation is Ell3 dependent

Video of Ali Shilatifard

You can read more here

No comments:

Post a Comment

Please note that we dont offer any kind of medical advice. Questions requesting specific medical advice (e.g. where can I get this treatment, will this cure XXX condition, etc) will be published but most probably ignored by the administrators. :)

Note to spammers: You shall not pass. If you really want a link from us then consider making a stem cell related guest post !