Navigation Links
Epigenetics enigma resolved

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
Emory Health Sciences

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:
Related Image:
Epigenetics enigma resolved
(Date:9/28/2015)... SAN FRANCISCO , September 28, 2015 ... size is expected to reach USD 12.03 billion by ... to 2020. Technological advancements such as Backside Illumination (BSI) ... revenue growth over the forecast period.      ... the back of the chip to reduce loss and, ...
(Date:9/24/2015)... , September 24, 2015 ... september 2015 Kerv ( ... finanstjänster, lanserar idag världens första kontaktlösa betalningsring ... in 77 000 GBP för massproduktion via ... ) , Kerv-bärare kan ...
(Date:9/10/2015)... 10, 2015  NXT-ID, Inc. (NASDAQ: NXTD ) ... on the growing mobile commerce market, announces that the ... Touch of Modern, will feature the Wocket® smart wallet ... . Touch Of Modern is ... lifestyle products to its 7.2 million members. Customers are ...
Breaking Biology News(10 mins):
(Date:10/12/2015)... , Oct.12, 2015  MiMedx Group, Inc. (NASDAQ: ... amniotic tissue and patent-protected processes to develop and market ... Orthopedic, Spine, Sports Medicine, Ophthalmic, and the Dental sectors ... had been filed against the Company has been dismissed ... , Chairman and CEO, stated, "As we suspected, this ...
(Date:10/12/2015)... , 12 de octubre de 2015 ... (D-CA) llegó a un récord en el congreso con ... anual de la International Plasma Awareness Week (IPAW), que ... IPAW está patrocinada por la Plasma Protein Therapeutics ... para: , Aumentar la concienciación mundial ...
(Date:10/12/2015)... , October 12, 2015 ... to print version for enriched online experience ... media alternative to print version for enriched online experience ... user-friendly, multi media alternative to print version for ... world-leading provider of scientific, technical and medical information products ...
(Date:10/12/2015)... , ... October 12, 2015 , ... LifeTrak , ... launch of LifeTrak Zoom, the world’s first amphibious fitness tracker that seeks to meet ... flexwear technology and accurate heart rate monitoring both in water and on ...
Breaking Biology Technology: