PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Epigenetics enigma resolved

First structure of enzyme that removes methylation

2013-12-27
(Press-News.org) Contact information: Quinn Eastman
qeastma@emory.edu
404-727-7829
Emory Health Sciences
Epigenetics enigma resolved First structure of enzyme that removes methylation

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 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 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.



INFORMATION:

The research was supported by the National Institute of General Medical Sciences (GM049245, GM095209, GM105132) and the Georgia Research Alliance.



ELSE PRESS RELEASES FROM THIS DATE:

Researchers complete a milestone in defining the genetic basis of rheumatoid arthritis

2013-12-27
Researchers complete a milestone in defining the genetic basis of rheumatoid arthritis MANHASSET, NY – An international group of investigators has discovered new genes, pathways and cell types that are involved in inherited susceptibility to rheumatoid ...

International team completes systematic, genomic study of cervical cancer

2013-12-27
International team completes systematic, genomic study of cervical cancer Findings point to potential therapeutics, shed light on HPV role Researchers from the Boston area, Mexico, and Norway have completed a comprehensive genomic analysis of cervical ...

New genetic risk factor for type 2 diabetes revealed

2013-12-27
New genetic risk factor for type 2 diabetes revealed Samples from Mexican, Latin American populations shed light on disease Cambridge and Boston, MA; Los Angeles, CA; Mexico City, Mexico. Wed. December 25, 2013 – An international team of researchers ...

Researcher says extensive use of antibiotics in agriculture creating public health crisis

2013-12-27
Researcher says extensive use of antibiotics in agriculture creating public health crisis University of Calgary's Aidan Hollis advocates user fees on non-human antibiotics use Citing an overabundance in the use of antibiotics by the agriculture and aquaculture industries ...

Rheumatoid arthritis research shows the potential of large-scale genetic studies for drug discovery

2013-12-27
Rheumatoid arthritis research shows the potential of large-scale genetic studies for drug discovery The results of the largest international study to date into the genetic basis of rheumatoid arthritis shed light on the biology of the disease and provide evidence that large-scale genetic ...

Special topic: Airworthiness and fatigue

2013-12-27
Special topic: Airworthiness and fatigue Aviation safety is the theme given to the International Conference on Airworthiness and Fatigue: 7th ICSAELS Series Conference, Beijing, China, held on 25 March, 2013. This event was initiated by the International Center of ...

Molecular markers used for assessment of early sciatic nerve injury

2013-12-27
Molecular markers used for assessment of early sciatic nerve injury Substance P and calcitonin gene-related peptide are the main neuropeptides in peripheral nerve ganglia, which can anterogradely transmit nociceptive information to the central nervous system. In ...

Genetic discovery points the way to much bigger yields in tomato, other flowering food plants

2013-12-27
Genetic discovery points the way to much bigger yields in tomato, other flowering food plants Scientists learn how tweaking a 'hybrid vigor' gene generates higher crop yields Cold Spring Harbor, NY – Every gardener knows the look of a ripe tomato. That bright ...

Building a better malaria vaccine: Mixing the right cocktail

2013-12-27
Building a better malaria vaccine: Mixing the right cocktail A safe and effective malaria vaccine is high on the wish list of most people concerned with global health. Results published on December 26 in PLOS Pathogens suggest how a leading vaccine ...

Gene therapy for human skin disease produces long-term benefits

2013-12-27
Gene therapy for human skin disease produces long-term benefits Stem cell-based gene therapy holds promise for the treatment of devastating genetic skin diseases, but the long-term clinical outcomes of this approach have been unclear. In a study online December 26th in the ...

LAST 30 PRESS RELEASES:

Sensing sickness

Cost to build multifamily housing in California more than twice as high as in Texas

Program takes aim at drinking, unsafe sex, and sexual assault on college campuses

Inability to pay for healthcare reaches record high in U.S.

Science ‘storytelling’ urgently needed amid climate and biodiversity crisis

KAIST Develops Retinal Therapy to Restore Lost Vision​

Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response

Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid

Low LDL cholesterol levels linked to reduced risk of dementia

Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients

Almost one in ten people surveyed report having been harmed by the NHS in the last three years

Enhancing light control with complex frequency excitations

New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients

New insight into factors associated with a common disease among dogs and humans

Illuminating single atoms for sustainable propylene production

New study finds Rocky Mountain snow contamination

Study examines lactation in critically ill patients

UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award

Doubling down on metasurfaces

New Cedars-Sinai study shows how specialized diet can improve gut disorders

Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana

PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation

ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy

How VR technology is changing the game for Alzheimer’s disease

A borrowed bacterial gene allowed some marine diatoms to live on a seaweed diet

Balance between two competing nerve proteins deters symptoms of autism in mice

Use of antifungals in agriculture may increase resistance in an infectious yeast

Awareness grows of cancer risk from alcohol consumption, survey finds

The experts that can outsmart optical illusions

Pregnancy may reduce long COVID risk

[Press-News.org] Epigenetics enigma resolved
First structure of enzyme that removes methylation