Navigation Links
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 Bloomberg 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 we see in cancer are leading cells to look and behave like other cells they're not at all supposed to be like," Feinberg says. "For example, colon cells that become cancerous might start to act like brain, liver or spleen cells. They're losing the characteristics they should have and taking on those of other tissues."

He and his colleagues suggest in the study, published online on Jan. 18 in Nature Genetics, that their newly developed map of where these methylation sites differ in colon cancer and healthy tissue may eventually help researchers develop treatments for cancer by restoring normal methylation patterns or by targeting the gene pathways they have identified in this study.


'/>"/>

Contact: Christen Brownlee
cbrownlee@jhmi.edu
410-955-7832
Johns Hopkins Medical Institutions
Source:Eurekalert

Related biology news :

1. Growth of new brain cells requires epigenetic switch
2. Burnham researchers discover on switch for cell death signaling mechanism
3. How chromosomes meet in the dark -- Switch that turns on X chromosome matchmaking
4. Researchers find natures shut-off switch for cellulose production
5. Women double fruit, veggie intake with switch to Mediterranean diet plan
6. New master switch found in the brain that regulates appetite and reproduction
7. Newly discovered molecular switch helps decide cell type in early embryo development
8. Miscanthus can meet US biofuels goal using less land than corn or switchgrass
9. Control switches found for immune cells that fight cancer, viral infection
10. A molecular switch turns on the flame in natures blowtorch
11. Berkeley researchers identify photosynthetic dimmer switch
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/7/2016)... 7, 2016   Veridium , a leader ... of new CEO James Stickland . Stickland, ... of experience, has served in senior executive roles ... specialized in expanding a pipeline of venture capital ... most recently served as managing director of U.K.-based ...
(Date:12/6/2016)... Valencell , the leading innovator in ... a third consecutive year of triple digit growth for ... with a 360 percent increase in companies who have ... driven by sales of its wrist and ear Benchmark™ ... technology for hearables for fitness and healthcare applications. ...
(Date:12/5/2016)... -- The Office of Justice Programs, National Institute of ... or Replace Medico Legal Autopsies?" on NIJ.gov.  The ... forensic autopsies with postmortem X-ray computed tomography, commonly ... to recommendations made by The National Academy of ... a potential component of medicolegal death investigations. NIJ,s ...
Breaking Biology News(10 mins):
(Date:12/7/2016)... and ANN ARBOR, Mich. , Dec. ... company developing breakthrough immune modulatory medicines, announced today the ... Company,s lead therapeutic candidate, LYC-30937- E nteric C ... debilitating skin disease that is estimated to affect as ... States , with approximately 1.5 - 3 million ...
(Date:12/7/2016)... , ... December 07, 2016 ... ... opening applications to an early access program for SmartBiome -- a novel ... with the simultaneous specific enrichment and detection of hundreds of different genes. ...
(Date:12/6/2016)... ... December 06, 2016 , ... ... 2016 asking the Federal Drug Administration (FDA) to consider OA as a serious ... is concerned about the growing population of OA patients, many of whom may ...
(Date:12/6/2016)... 2016 According to a new market research ... Glass, Silicon), Application (Genomics, Proteomics, Capillary Electrophoresis, POC, Clinical, Environmental, Drug ... market is projected to reach USD 8.78 Billion by 2021 from ... the forecast period (2016 to 2021). ... ...
Breaking Biology Technology: