Navigation Links
Epigenetics enigma resolved
Date:12/25/2013

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."

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, are scheduled for publication 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 chromatographymass 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 the "off" signal provided by 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; understanding how that domain works will be a new puzzle opened up by having the Naegleria structure, Cheng says.


'/>"/>

Contact: Quinn Eastman
qeastma@emory.edu
404-727-7829
Emory Health Sciences
Source:Eurekalert  

Related biology news :

1. Epigenetics by Lyle Armstrong -- Now available
2. Ludwig presents advancements in immunotherapy and epigenetics at the American Association for Cancer Research Annual Meeting
3. Ludwig advancements in immunotherapy and epigenetics top scientific program at AACR
4. Epigenetics studies take root in plants
5. Epigenetics mechanism may help explain effects of moms nutrition on her childrens health
6. Life experiences put their stamp on the next generation: New insights from epigenetics
7. Epigenetics shapes fate of brain vs. brawn castes in carpenter ants
8. Study finds epigenetics, not genetics, underlies homosexuality
9. Sick from stress? Blame your mom… and epigenetics
10. Not by DNA alone: How the epigenetics revolution is fostering new medicines
11. Epigenetics and epidemiology -- hip, hype and science
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Epigenetics enigma resolved
(Date:4/19/2016)... UAE, April 20, 2016 The ... as a compact web-based "all-in-one" system solution for all ... fingerprint reader or the door interface with integration authorization ... access control systems. The minimal dimensions of the access ... into the building installations offer considerable freedom of design ...
(Date:4/15/2016)... , April 15, 2016 ... the,  "Global Gait Biometrics Market 2016-2020,"  report to ... http://photos.prnewswire.com/prnh/20160330/349511LOGO ) , ,The global gait biometrics ... of 13.98% during the period 2016-2020. ... angles, which can be used to compute factors ...
(Date:4/13/2016)... CHICAGO , April 13, 2016  IMPOWER physicians ... are setting a new clinical standard in telehealth ... By leveraging the higi platform, IMPOWER patients can ... weight, pulse and body mass index, and, when they ... quick and convenient visit to a local retail location ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , June 23, 2016 Houston Methodist ... the Cy-Fair Sports Association to serve as their ... agreement, Houston Methodist Willowbrook will provide sponsorship support, ... connectivity with association coaches, volunteers, athletes and families. ... the Cy-Fair Sports Association and to bring Houston ...
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the ... the Supplyframe Design Lab . Located in Pasadena, Calif., the Design Lab’s ... how hardware projects are designed, built and brought to market. , The Design ...
(Date:6/23/2016)... 2016 Andrew D ... http://doi.org/10.17925/OHR.2016.12.01.22 Published recently in ... from touchONCOLOGY, Andrew D Zelenetz , discusses ... care is placing an increasing burden on healthcare ... therapies. With the patents on many biologics expiring, ...
(Date:6/23/2016)... -- Amgen (NASDAQ: AMGN ) today announced a ... sciences incubator to accelerate the development of new therapies ... QB3@953 was created to help high-potential life science and ... stage organizations - access to laboratory infrastructure. ... "Amgen Golden Ticket" awards, providing each winner with one ...
Breaking Biology Technology: