( ill be scaled up to learn more about th...)In a technical tour de force, Salk scientists take a global view of the epigenome

The approach developed by Ecker and collaborators may allow researchers to do just that. "We fit the whole Arabidopsis genome - about 120 million bases - on a single high density microarray," says Ecker. "To look at the entire human genome you would just need six more chips."

Each microarray or DNA chip is dotted with 6 million short DNA fragments that span the Arabidopsis genome like floor tiles. The researchers first isolated all methylated DNA from plant cells and located where those fragments fell on the array. Then they determined which genes were active and which ones weren't in order to compare gene activation with the methylation pattern.

The investigators saw significant changes when they compared activity of genes in normal plants with gene activity in plant mutants unable to methylate DNA. "It was pretty dramatic. There are hundreds of genes that you never see expressed except in methylation mutants," says Ecker.

Almost a third of Arabidopsis' ~ 26,000 genes were methylated in some manner, and where they were methylated determined the effect. As in mammals, methylation in regulatory regions next to genes generally silenced genes. However, methylation across the body of a gene appeared to correlate with higher expression.

Different cell types show different methylation patterns. DNA methylation in stem cells differs from that in a mature skin or nerve cell. Part of the makeover mature cells must undergo for therapeutic cloning purposes will likely involve remodeling methylation patterns to resemble those of stem cells. And disease states, ranging from retardation to cancer, are marked by aberrant methylation: some carcinogens cause cancer by methylating the "wrong" genes, leading to uncontrolled growth.

Once a cell's DNA methylation pattern - be it normal or pathological - is established, methylated sites are faithfully inher
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Source:Salk Institute