Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Hopkins Team Discovers How DNA Changes

Newly revealed process has implications for understanding cancers, psychiatric disorders and neurodegenerative diseases

Using human kidney cells and brain tissue from adult mice, Johns Hopkins scientists have uncovered the sequence of steps that makes normally stable DNA undergo the crucial chemical changes implicated in cancers, psychiatric disorders and neurodegenerative diseases. The process may also be involved in learning and memory, the researchers say.

A report on their study appears online April 14 in Cell.

While DNA is the stable building block of all of an individual’s genetic code, or genome, the presence or absence of a methyl group at specific locations chemically alters DNA and changes the expression of the genes. In a series of experiments, the Johns Hopkins team identified a step-by-step process involving a previously unknown step and two molecules for DNA to change from a methylated to demethylated state. Both methylation and demethylation have long been linked to genetic alterations and a wide range of diseases.

“Anything we can learn from these studies about how to manipulate the process of changing DNA methylation status is going to have implications for human development and disease, including cancer and degenerative disorders,” says Hongjun Song, Ph.D., professor of neurology and neuroscience and director of the Stem Cell Program in the Institute for Cell Engineering, the Johns Hopkins University School of Medicine.

First, using human kidney cells in a dish, the Hopkins team focused its investigation on a tiny region of DNA in the cells’ nuclei, specifically watching the actions of one particular chemical base known as cytosine (C). The team added different chemicals to force methylation changes and after watching the fate of methylated cytosine (mC) for two days, and noting that nothing had changed, they then added a protein called TET1 to the cell. As a result, some of the mC became hydroxylmethylated (hmC) and some reverted to plain C, indicating loss of the methyl-group from C in the DNA.

“What this told us was TET1 promotes this process of DNA changing status from methylated to demethylated,” Song says.

While only about five percent of human cells progress from hmC to C under natural conditions, the researchers found they could enhance the demethylation process by adding another protein called Apobec1.

“That suggested another clear step in DNA demethylation,” Song says. “Cells go from mC to hmC by TET1, and then from hmC to C involving Apobec 1.”

Next, they followed up on their own previously published work showing that electrical stimulation like that used in electroconvulsive therapy (ECT) resulted in increased brain cell growth in mice, which likely was an effect of changes in DNA methylation status. The researchers used a genetic tool and PCR-based approach to amplify a tiny region of the genome in dozens of mice, some exposed to ECT-like electrical stimulation and some not, to compare the status of cytosine at similar stretches of DNA in brain tissue. By using genetic sequencing technology to analyze the various states of methylation – simple C, methylated C, or hydroxylmethlyated Cs – in the specific reigons of DNA from brain cells of ECT-exposed mice versus other animals, they found evidence that ECT indeed induces DNA demethylation and identified TET1 as a critical factor for this to happen.

“By identifying two molecules and tying together two pathways needed for DNA methylation status to change, we believe we have shown a unified mechanism that regulates DNA as it goes from a methylated state to a demethylated state,” Song says. “This new knowledge gives us an entry point to someday manipulating this fundamentally important process for treating patients with diseases associated with epigenetic abnormality.”

Support for this research came from the National Institutes of Health, Johns Hopkins Brain Science Institute, National Alliance for Research on Schizophrenia and Depression, and Adelson Medical Research Foundation

Authors of the paper, in addition to Hongjun Song are Junjie U. Guo, Yijing Su, Chun Zhong, and Guo-li Ming, all of Johns Hopkins.

On the Web:
Song lab:

Maryalice Yakutchik | Newswise Science News
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>