Researchers find spots where our body switches off defective genes

January 19th, 2009 - 2:32 pm ICT by IANS  

Washington, Jan 19 (IANS) A startling discovery made by scientists vastly enlarges the scope of understanding diseases and cancers, opening up new ways of treating them. Researchers have found the places in the human genome at which our body shuts down genes when it wants to get rid of them.Scientists studying how the body shuts down genes have tended to focus on small DNA islets, 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 discovered 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,” said Andrew Feinberg, professor of medicine at the Johns Hopkins University School of Medicine.

Feinberg explained that the discovery is significant since it may shift the current focus away from the islands to thousands of new sites scattered throughout the genome.

Each of them has the potential to serve as novel targets for studying the development of tissues, organs and animals, and for treating diseases like 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.

However, Feinberg and co-investigator Rafael I. Irizarri, of Johns Hopkins and 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 the 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.

In contrast, only six percent of methylated sites were situated inside the islands. Because of the newly discovered sites’ proximity to the islands, the researchers named them shores, said a Hopkins release.

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