Featured Research

from universities, journals, and other organizations

New labeling method expands ability to read DNA modification

Date:
December 15, 2010
Source:
Emory University
Summary:
Researchers have developed a method for labeling and mapping a "sixth nucleotide," whose biological role scientists are only beginning to explore. The method allowed the researchers to see for the first time how 5-hydroxymethylcytosine (5-hmC) is distributed throughout the genome.

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.

Related Articles


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.

The research was supported by the National Institutes of Health.


Story Source:

The above story is based on materials provided by Emory University. The original article was written by Quinn Eastman. Note: Materials may be edited for content and length.


Journal Reference:

  1. Chun-Xiao Song, Keith E Szulwach, Ye Fu, Qing Dai, Chengqi Yi, Xuekun Li, Yujing Li, Chih-Hsin Chen, Wen Zhang, Xing Jian, Jing Wang, Li Zhang, Timothy J Looney, Baichen Zhang, Lucy A Godley, Leslie M Hicks, Bruce T Lahn, Peng Jin, Chuan He. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nature Biotechnology, 2010; DOI: 10.1038/nbt.1732

Cite This Page:

Emory University. "New labeling method expands ability to read DNA modification." ScienceDaily. ScienceDaily, 15 December 2010. <www.sciencedaily.com/releases/2010/12/101213091014.htm>.
Emory University. (2010, December 15). New labeling method expands ability to read DNA modification. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2010/12/101213091014.htm
Emory University. "New labeling method expands ability to read DNA modification." ScienceDaily. www.sciencedaily.com/releases/2010/12/101213091014.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins