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Large DNA stretches, not single genes, shut off as cells mature
Date:1/18/2009

Experiments at Johns Hopkins have found that the gradual maturing of embryonic cells into cells as varied as brain, liver and immune system cells is apparently due to the shut off of several genes at once rather than in individual smatterings as previous studies have implied.

Working with mouse brain and liver cells, as well as embryonic stem cells, Johns Hopkins University School of Medicine professor Andrew Feinberg, M.D., M.P.H., led an investigation of a kind of epigenetic modification to histones, the molecular "spools" that DNA winds around in the cell nucleus. This modification is a variety of the so-called epigenetic changes that alter the function of cells without directly altering the nuclear DNA in the cells.

Other scientists had previously found that histone modifications appear to silence individual genes in the DNA that coils around affected histones. But when Feinberg and his team compared the activity of thousands of genes in the liver and brain cells, they found that a particular modification in which two methyl groups clip onto histones seemed to silence long stretches of DNA containing many genes at once. The findings will publish in Nature Genetics online on Jan. 18.

Since the silenced stretches varied greatly between the different types of cells, Feinberg, postdoctoral fellow Bo Wen, and their colleagues wondered whether these sections called large organized chromatin K9 modifications, or LOCKS might be responsible for the transition from the "blank slate" quality of embryonic cells to the specialized functions that mature cells take on. To find out, he and his team looked for LOCKs in mouse embryonic stem cells. Unlike mature, adult liver and brain cells, in which about 40 percent of the genome was silenced by LOCKs, the embryonic stem cells had no LOCKs.

Next, the researchers compared the regions of DNA affected by LOCKs between mouse liver and brain cells and their corresponding human cel
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Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

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