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Rules governing expression of developmental genes in mouse embryonic stem cells are more nuanced than anticipated

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Posted August 12, 2013
A detailed analysis of the methylation patterns of histone H3 revealed a nuanced picture of the epigenetic rules governing expression of developmental genes in mouse embryonic stem cells. The image shows a ChIP-seq track file example of H3K4me3 at mouse Homeobox (Hox) gene clusters. Credit: Study's authors and Nature Structure & Molecular Biology.

A detailed analysis of the methylation patterns of histone H3 revealed a nuanced picture of the epigenetic rules governing expression of developmental genes in mouse embryonic stem cells. The image shows a ChIP-seq track file example of H3K4me3 at mouse Homeobox (Hox) gene clusters. Credit: Study’s authors and Nature Structure & Molecular Biology.

A decade ago, gene expression seemed so straightforward: genes were either switched on or off. Not both. Then in 2006, a blockbuster finding reported that developmentally regulated genes in mouse embryonic stem cells can have marks associated with both active and repressed genes, and that such genes, which were referred to as “bivalently marked genes”, can be committed to one way or another during development and differentiation.

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.”

A study by researchers at the Stowers Institute for Medical Research now revisits that notion. In this week’s advance online edition of the journal Nature Structural and Molecular Biology, a team led by Investigator Ali Shilatifard, Ph.D., identifies the protein complex that implements the activating histone mark specifically at “poised” genes in mouse embryonic stem (ES) cells, but reports that its loss has little effect on developmental gene activation during differentiation. This suggests that there is more to learn about interpreting histone modification patterns in embryonic and even cancer cells.

 

Read more at: Phys.org

 

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