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

erg School of Public Health, and their colleagues wondered whether undiscovered methylated sites were hiding unnoticed elsewhere in the genome. The researchers performed their comprehensive survey in human brain, liver and spleen tissues obtained from five autopsies, identifying 16,379 methylated regions using a new method that searches all DNA, not just CpG islands.

To their surprise, the researchers discovered that about 76 percent of the genome's methylated sites occur a short distance away from the islands, between 200 and 2,000 kilobases away. In contrast, only 6 percent of methylated sites were situated inside CpG islands. Because of the newly discovered sites' proximity to the islands, the researchers named them CpG shores.

"This finding is so unexpected because CpG islands are the areas where scientists have really concentrated their research," Feinberg says.

Taking their research a step further, Feinberg, Irizarri and their colleagues searched for new methylated areas in colon tumors as well as normal colon tissue removed from 13 different cancer patients. The researchers identified 2,707 regions in both CpG islands and shores that were either more or less methylated between the two tissue types. Previous studies by other research groups, looking only at CpG islands, have suggested that the DNA in cancer cells tends to be more methylated compared to normal, healthy cells. However, comparing the tumor and healthy colon cells' entire genomes, including CpG islands as well as shores, Feinberg's group found that cancer cells had a roughly equal number of more-methylated and less-methylated sites than the normal cells.

When the researchers looked at where these differently methylated sites were located in the cancer cells, they found that these regions matched up with many of the methylated areas they'd located in the normal brain, liver and spleen tissues they had examined.

"This suggests that the epigenetic changes
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Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

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