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Gene switch sites found mainly on 'shores,' not just 'islands' of the human genome
Date:1/18/2009

Scientists who study how human chemistry can permanently turn off genes have typically focused on small islands of DNA believed to contain most of the chemical alterations involved in those switches. But after an epic tour of so-called DNA methylation sites across the human genome in normal and cancer cells, Johns Hopkins scientists have found that the vast majority of the sites aren't grouped in those islands at all, but on nearby regions that they've named "shores."

"Our study suggests that the real jackpot for methylation isn't where we have all been looking, but in these shores located just nearby," says Andrew Feinberg, M.D., M.P.H., professor of medicine at the Johns Hopkins University School of Medicine.

Feinberg explains that the discovery is more than academic since it may shift the current focus away from the islands to thousands of new sites scattered throughout the genome, each with the potential to serve as novel targets for studying the development of tissues, organs and animals, and for treating diseases such as cancer already known to involve methylation chemistry.

Methylation is one of several so-called epigenetic modifications that affect which genes are expressed without changing the DNA sequence itself. Previous studies have suggested that DNA methylation plays an important role in guiding stem cells to mature into a variety of cell types such as hair, muscle and nerve cells. Methylation has also been implicated in the abnormal gene expression that cancer cells show.

The long-time focus in methylation has been CpG islands, regions of the genome rich in the DNA building-block molecules cytosine and guanine. The reason is that these islands tend to occur near the "start" signal of a protein-coding gene, a place with the potential to affect whether that gene is expressed or not and to what extent.

However, Feinberg and co-investigator Rafael I. Irizarri, Ph.D., of the Johns Hopkins University Bloomb
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Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

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