Navigation Links
New labeling method expands ability to read DNA modification
Date:12/13/2010

Researchers at Emory University School of Medicine and the University of Chicago have developed a method for labeling and mapping a "sixth nucleotide," whose biological role scientists are only beginning to explore.

The method is described online this week in Nature Biotechnology.

The method allowed the researchers to see for the first time how 5-hydroxymethylcytosine (5-hmC) is distributed throughout the genome. Unlike 5-methylcytosine (5-mC), a chemical modification of DNA that is generally found on genes that are turned off, this extra layer of modification is enriched in active genes. 5-hmC appears to be more abundant in embryonic stem cells and brain cells, compared with other cell types, and its abundance increases substantially as the brain matures.

"The main reason why this DNA modification was not explored previously was because standard approaches didn't detect it. The groups that identified it had to isolate large amounts of DNA and analyze it directly," says co-senior author Peng Jin, PhD, professor of human genetics at Emory University School of Medicine. "I think the beauty of this work lies in how we combined an innovation in DNA chemistry with large-scale genetic analysis to achieve new insight."

In recent years, scientists have been examining the role of methylation, a modification of cytosine, one of the four bases that make up DNA (adenine, thymine, guanine are the others). When stem cells change into the cells that make up skin, blood, muscle or brain, DNA methylation helps shut inappropriate genes off. Changes in DNA methylation also underpin a healthy cell's transformation into a cancer cell.

In 2009, a second layer of modification on top of 5-mC emerged, with the discovery that 5-hmC was present in mouse brain and especially abundant in Purkinje cells, which are part of the cerebellum. While previous researchers had reported the presence of 5-hmC in human and animal DNA samples, current methods did not allow them to distinguish between 5-mC and 5-hmC.

Seeking to fill this gap, a team at the University of Chicago led by Chuan He, PhD, professor of chemistry, exploited the properties of an enzyme from a bacterial phage, which can attach a chemically modified sugar tag to 5-hmC. They collaborated with Jin, postdoc Keith Szulwach and colleagues to map where 5-hmC appears in the genome and in various cell types.

While the chemical labeling method allows the separation of DNA containing 5-hmC from other DNA, it does not yet provide the ability to see 5-mhC when DNA is read letter-by-letter. He, Jin and their colleagues are working on a higher resolution method for finer analysis.

Mouse embryonic stem cell DNA contains 5-hmC at a level of 500 parts per million, the researchers found. In a mouse's cerebellum, the level rises from 1000 to 4000 parts per million as the mouse becomes an adult and that part of the brain matures. In contrast to 5-mC, which is generally found on genes that are turned off, 5-hmC is enriched on active genes, the researchers found.

"This specific gene enrichment suggests that it is not just an intermediate step when cells need to get rid of DNA methylation, but it may have a unique function in gene regulation," Jin says.

Mutations in the enzymes responsible for converting 5-mC to 5-hmC have also been linked to a form of leukemia, he notes.

The team looked to see which genes tend to acquire 5-hmC as the brain ages, and found an enrichment for genes involved with neurodegeneration, the cell's response to low oxygen and growth of new blood vessels.

"Because the enzymes that convert 5-mC into 5-hmC require oxygen, this may be another way that cells sense and respond to oxygen levels and oxidative stress," Jin says.


'/>"/>

Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

Related biology news :

1. Restaurant and packaged foods can have more calories than nutrition labeling indicates
2. Laser etching safe alternative for labeling grapefruit
3. Basic guides to PCR, labeling neurons featured in Cold Spring Harbor Protocols
4. MGH researchers develop faster method of engineering zinc-finger nucleases
5. Researcher develops accurate method for detecting dangerous fluoride
6. Shotgun method allows scientists to dissect cells sugar coatings
7. New low-cost method to deliver vaccine shows promise
8. Fast-track gene-ID method speeds rare disease search
9. OU study on genetics in fruit flies leads to new method for understanding brain function
10. New method successfully predicted how oil from Deepwater Horizon spill would spread
11. University at Buffalo symposium on in silico methods, high throughput screening
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2017)... 2017 Research and Markets has announced the ... Trends - Industry Forecast to 2025" report to their offering. ... The Global ... of around 8.8% over the next decade to reach approximately $14.21 ... market estimates and forecasts for all the given segments on global ...
(Date:3/22/2017)... 2017 Vigilant Solutions , a vehicle ... agencies, announced today the appointment of retired FBI special ... safety business development. Mr. Sheridan brings more ... a focus on the aviation transportation sector, to his ... Mr. Sheridan served as the Aviation Liaison Agent Coordinator ...
(Date:3/16/2017)... March 16, 2017 CeBIT 2017 - Against identity fraud with DERMALOG ... ... Used combined in one project, multi-biometric solutions provide a crucial contribution ... Used combined in one ... ...
Breaking Biology News(10 mins):
(Date:3/22/2017)... MONICA, Calif. , March 22, 2017 /PRNewswire/ ... are proud to announce their extended partnership and ... will be headlined by the 21 st ... BIOMEDevice Boston, taking place May 3-4, 2017. ... Advanced Medical Technology Association (ADVAMED) President and CEO, ...
(Date:3/22/2017)... 2017 The global chronic kidney ... report by Transparency Market Research (TMR). The top four ... AbbVie Inc., accounted for a share of only 41.4% ... this market are focusing aggressively on mergers, acquisitions, and ... likely to lead to market consolidation in the next ...
(Date:3/22/2017)... 22, 2017   VWR (NASDAQ: ... product and service solutions to laboratory and ... acquired EPL Archives, Inc., an international biorepository ... entire regulated product research, development and commercialization ... and ancillary services. EPL Archives is widely ...
(Date:3/22/2017)... ... March 21, 2017 , ... Benchworks CEO ... Executive Officer Forum on March 23-24 in San Diego. The event is a ... diagnostic industries. , Benchworks Vice President Christian Meyer will also participate in the ...
Breaking Biology Technology: