Main Category: Stem Cell Research
Also Included In: Genetics
Article Date: 13 Aug 2013 – 1:00 PDT
Stowers Institute for Medical Research
The Mll2 branch of the COMPASS family regulates bivalent promoters in mouse embryonic stem cells
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Rules governing expression of developmental genes in mouse embryonic stem cells are more nuanced than anticipated
This paradoxical state – akin to figuring out how to navigate a red and green traffic signal – has since undergone scrutiny by labs worldwide. What has been postulated is that the control regions (or promoters) of some genes, particularly those critical for development during the undifferentiated state, stay “poised” for plasticity by communicating with both activating and repressive histones, a state biologists term “bivalency.”
The revelation came when the researchers evaluated behaviors of Mll2-deficient mouse embryonic stem cells. First, the cells continued to display the defining property of a stem cell, the ability to “self-renew,” meaning that genes that permit stem cell versatility were undisturbed by Mll2 loss. But remarkably, when cultured with a factor that induces their maturation, Mll2-deficient mouse ES cells showed no apparent abnormalities in gene expression. In fact, expression of the very Hox genes that normally exhibit bivalent histone marks was as timely in Mll2-deficient cells as it was in non-mutant cells.
“There has been a lot of excitement over the idea that promoters of developmentally regulated genes exhibit both the stop and go signals,” explains Shilatifard. “That work supports the idea that histone modifications could constitute a code that regulates gene expression. However, we have argued that the code is not absolute and is context dependent.”
Stowers Institute for Medical Research. “Rules governing expression of developmental genes in mouse embryonic stem cells are more nuanced than anticipated.” Medical News Today. MediLexicon, Intl., 13 Aug. 2013. Web.
13 Aug. 2013. <http://www.medicalnewstoday.com/releases/264696.php>
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Funding for the study came from the Stowers Institute for Medical Research and the United States National Cancer Institute.
“This means that Mll2-deficient mouse ES cells that receive a differentiation signal can still activate genes required for maturation, even though they have lost the H3K4me3 mark on bivalent regions” says Deqing Hu, Ph.D., the postdoctoral fellow who led the study. “This work paves the way for understanding what the real function of bivalency is in pluripotent cells and development.”
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