Life's imprint on DNA now mappable in single cell

Date: Jul-21-2014 Researchers in the UK have developed a powerful new technique that uses a single cell to map the epigenetic marks

that life leaves on our DNA. The development is considered a breakthrough

because it will allow scientists to better understand the effect of environment on DNA, such as

during the early life of the embryo, and in the development of diseases like cancer.

The team, comprising members from the Babraham Institute - a research center funded by the

Biotechnology and Biological Sciences Research Council (BBSRC) - and the Wellcome Trust Sanger

Institute, both in Cambridge, reports its findings in the journal Nature Methods.

The fusing of sperm and egg produces a new organism with its own DNA, the fundamental boiler-plate of instructions on how growth and development should unfold. But recently in the

history of DNA research, scientists have discovered there is another layer of instructions over

the DNA boiler-plate - "epigenetic marks" or chemical tags that annotate the DNA.

Epigenetic map is a 'cellular memory'

Epigenetic marks alter gene behavior according to environmental conditions. Now, researchers say there is an epigenetic map that acts as a cellular memory.

Epigenetic marks do not change the underlying DNA sequence, but they add extra instructions

that do various things like silence certain genes and switch others on to differentiate a

skin cell from a brain cell; they also alter gene behavior according to environmental

conditions.

Thus, as well as DNA itself, there is an epigenetic map that acts as a kind of "cellular

memory" of a cell's experience and response to environmental conditions.

This memory is preserved long after the condition in the environment that triggered it has faded. For example, a change in diet might result in a change in the epigenetic map and influence the long-term health of the organism.

Scientists are starting to realize that epigenetics research is as important to understanding

health and disease as the study of the underlying DNA. But the tools to do this are not ideal.

Researchers have had to rely on using mice as models for human early development, and tissue for

analysis is very restricted.

New technique offers 'unprecedented ability to study epigenetic processes'

The ability to study the map of all the epigenetic marks of a person by using just a single

cell is a significant step forward and gives researchers an "unprecedented ability to study

epigenetic processes," explains corresponding author Dr. Gavin Kelsey, from the Babraham

Institute:

"The ability to capture the full map of these epigenetic marks from individual cells will be

critical for a full understanding of early embryonic development, cancer progression and aid the

development of stem cell therapies."

The team expects such an application may potentially reduce the number of mice currently used

for epigenetic research.

One of the chemical processes that produce epigenetic marks is called DNA methylation, where

a methyl tag is attached to the DNA. The method the researchers describe in their paper treats

the DNA with bisulfite to locate all the epigenetic methylation marks across the whole

genome.

The treated DNA is then amplified and read using high-throughput gene sequencers that show the

locations of the methylation marks and the genes affected.

For the first time, researchers can track what happens in individuals cells

Current methods look for epigenetic marks in groups of cells. This means trying to track what

has happened in an individual cell is not clear. The new technique allows researchers to follow

what happens in individual cells at a critical time in the early development of an embryo - when each cell has the potential to develop in a unique way.

Using their new technique, the team has already found many of the epigenetic marks that

are different between cells are in places that control gene activity.

Dr. Kelsey says the proof-of-principle study shows that "large-scale, single-cell epigenetic

analysis is achievable to help us understand how epigenetic changes control embryonic

development."

"The application of single-cell approaches to epigenetic understanding goes far beyond basic

biological research," he adds. "Future clinical applications could include the analysis of

individual cancer cells to provide clinicians with the information to tailor treatments, and

improvements in fertility treatment by understanding the potential for epigenetic errors in

assisted reproduction technologies."

Funding for the study came from the BBSRC, the Medical Research Council (MRC), the Wellcome

Trust, EU Blueprint and EU EpiGeneSys.

Medical News Today also recently learned how Stanford researchers have taken the

first step in developing a tool that maps the origin of cancer from biological

signatures. The team believes the tool, which traces the origin of certain types of cancer

from the biological signature of their mutated cells, will help doctors decide the best

treatments for their patients.

Written by Catharine Paddock PhD

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.