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Control of gene expression: Histone occupancy in your genome
Date:4/30/2012

KANSAS CITY, MOWhen stretched out, the genome of a single human cell can reach six feet. To package it all into a tiny nucleus, the DNA strand is tightly wrapped around a core of histone proteins in repeating unitseach unit known as a nucleosome. To allow access for the gene expression machinery the nucleosomes must open up and regroup when the process is complete.

In the May 1, 2012, issue of Genes & Development, researchers at the Stowers Institute for Medical Research demonstrate how failure to restore order has lasting consequences. During the process of gene expression, a factor known as Chd1 promotes nucleosome reassembly on the DNA strand. Without it, yeast cells are unable to attach a chemical mark called ubiquitin to one of the four types of histone proteins, which in turn hampers nucleosome re-establishment throughout the entire yeast genome. In mammalian cells, this important step could be perturbed in disease states such as cancer.

"We have used the yeast Saccharomyces cerevisiae as a model system to study histone mono-ubiquitination and found that the mechanism is conserved in human cells," says Stowers Investigator Ali Shilatifard, Ph.D., who led the study. Why that's important dates back to studies initiated a decade ago on a gene called MLL, which is involved in the development of an aggressive type of leukemia in infants.

Previously, when Shilatifard's group analyzed the yeast version of MLL, they found that it enzymatically modified a histone called H3 by decorating it with a biochemical flag. In this case, that flag was not an ubiquitin, but rather a methyl group. Genes occupied by nucleosomes containing methylated H3 are generally switched on. Later, the lab confirmed that the same histone methylase activity was evolutionarily conserved from yeast to human cells, setting the stage for the molecular analysis of MLL activity in yeast.

The current study is based on a concept known as "histone c
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Contact: Gina Kirchweger
gxk@stowers.org
816-806-1036
Stowers Institute for Medical Research
Source:Eurekalert  

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