Featured Research

from universities, journals, and other organizations

Epigenetics enigma resolved

Date:
December 26, 2013
Source:
Emory Health Sciences
Summary:
Scientists have obtained the first detailed molecular structure of a member of the Tet family of enzymes. The finding is important for the field of epigenetics because Tet enzymes chemically modify DNA, changing signposts that tell the cell's machinery "this gene is shut off" into other signs that say "ready for a change."

Structure of Tet enzyme interacting with DNA, determined by X-ray crystallography. The active site, where the enzyme acts on the DNA, is close to the purple sphere. We can also see how binding the enzyne sharply bends the DNA double helix.
Credit: Emory Health Sciences

Scientists have obtained the first detailed molecular structure of a member of the Tet family of enzymes.

Related Articles


The finding is important for the field of epigenetics because Tet enzymes chemically modify DNA, changing signposts that tell the cell's machinery "this gene is shut off" into other signs that say "ready for a change."

Tet enzymes' roles have come to light only in the last five years; they are needed for stem cells to maintain their multipotent state, and are involved in early embryonic and brain development and in cancer.

The results, which could help scientists understand how Tet enzymes are regulated and look for drugs that manipulate them, were published online on Dec. 25 in Nature.

Researchers led by Xiaodong Cheng, PhD, determined the structure of a Tet family member from Naegleria gruberi by X-ray crystallography. The structure shows how the enzyme interacts with its target DNA, bending the double helix and flipping out the base that is to be modified.

"This base flipping mechanism is also used by other enzymes that modify and repair DNA, but we can see from the structure that the Tet family enzymes interact with the DNA in a distinct way," Cheng says.

Cheng is professor of biochemistry at Emory University School of Medicine and a Georgia Research Alliance Eminent Scholar. The first author of the paper is research associate Hideharu Hashimoto, PhD. A team led by Yu Zheng, PhD, a senior research scientist at New England Biolabs, contributed to the paper by analyzing the enzymatic activity of Tet using liquid chromatography-mass spectrometry.

Using oxygen, Tet enzymes change 5-methylcytosine into 5-hydroxymethylcytosine and other oxidized forms of methylcytosine. 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) are both epigenetic modifications of DNA, which change how DNA is regulated without altering the letters of the genetic code itself.

5-mC is generally found on genes that are turned off or on repetitive regions of the genome. 5-mC helps shut off genes that aren't supposed to be turned on (depending on the cell type) and changes in 5-mC's distribution underpin a healthy cell's transformation into a cancer cell.

In contrast to 5-mC, 5-hmC appears to be enriched on active genes, especially in brain cells. Having a Tet enzyme form 5-hmC seems to be a way for cells to erase or at least modify 5-mC, although the functions of 5-hmC are an active topic of investigation, Cheng says.

Alterations of the Tet enzymes have been found in forms of leukemia, so having information on the enzymes' molecular structure could help scientists design drugs that interfere with them.

N. gruberi is a single-celled organism found in soil or fresh water that can take the form of an amoeba or a flagellate; its close relative N. fowleri can cause deadly brain infections. Cheng says his team chose to study the enzyme from Naegleria because it was smaller and simpler and thus easier to crystallize than mammalian forms of the enzyme, yet still resembles mammalian forms in protein sequence.

Mammalian Tet enzymes appear to have an additional regulatory domain that the Naegleria forms do not; working out how that domain functions will be a new puzzle opened up by having the Naegleria structure, Cheng says.


Story Source:

The above story is based on materials provided by Emory Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hideharu Hashimoto, June E. Pais, Xing Zhang, Lana Saleh, Zheng-Qing Fu, Nan Dai, Ivan R. Corrκa, Yu Zheng, Xiaodong Cheng. Structure of a Naegleria Tet-like dioxygenase in complex with 5-methylcytosine DNA. Nature, 2013; DOI: 10.1038/nature12905

Cite This Page:

Emory Health Sciences. "Epigenetics enigma resolved." ScienceDaily. ScienceDaily, 26 December 2013. <www.sciencedaily.com/releases/2013/12/131226115340.htm>.
Emory Health Sciences. (2013, December 26). Epigenetics enigma resolved. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2013/12/131226115340.htm
Emory Health Sciences. "Epigenetics enigma resolved." ScienceDaily. www.sciencedaily.com/releases/2013/12/131226115340.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Classic Hollywood Memorabilia Goes Under the Hammer

Classic Hollywood Memorabilia Goes Under the Hammer

Reuters - Entertainment Video Online (Nov. 26, 2014) — The iconic piano from "Casablanca" and the Cowardly Lion suit from "The Wizard of Oz" fetch millions at auction. Sara Hemrajani reports. Video provided by Reuters
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
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) — The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Feast Your Eyes: Lamb Chop Sent Into Space from UK

Feast Your Eyes: Lamb Chop Sent Into Space from UK

Reuters - Light News Video Online (Nov. 25, 2014) — Take a stab at this -- stunt video shows a lamb chop's journey from an east London restaurant over 30 kilometers into space. Rough Cut (no reporter narration). Video provided by Reuters
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

 

Plants & Animals

Earth & Climate

Fossils & Ruins

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