Nanofluidics Identify Epigenetic Changes One Molecule at a Time

March 30, 2010

( -- Using a system of nanofluidic channels and multicolor fluorescence microscopy, a team of investigators at Cornell University has developed a method that analyzes the binding of DNA and DNA-binding proteins known as histones at specific locations along individual DNA molecules. The data generated using this method provides information on the so-called epigenetic state of a cell, which reflect differences in the genes that a given cell is expressing at any one time.

This research effort was led by Paul Soloway, Ph.D., and Harold Craighead, Ph.D., who is also the principle investigator of the Cornell University Physical Sciences-Oncology Center, one of eight newly established centers funded by the National Cancer Institute to identify and study the physical and biological laws and principles that guide the development and spread of cancer. The investigators published the results of this project in the journal Analytical Chemistry.

Every cell in the body contains the same , but what differentiates a liver cell from a heart cell is a series of DNA modifications, such as methylation, that determines the specific set of genes that are expressed in a specific type of cell. These modifications are known as epigenetic, rather than genetic, changes since they don't alter DNA's sequence, just its structural properties. Those structural changes determine which genes are accessible to the many proteins involved in turning into specific proteins.

There are many techniques that researchers can use to probe such epigenetic changes, but these methods require large numbers of cells, and thus, produce an average picture of epigenetic state. In addition, these techniques cannot survey the entire genome, nor can they examine two different types of epigenetic changes simultaneously.

To solve these limitations, the Cornell team created a nanofluidic device capable of flowing individual DNA molecules through a channel and past a detector that can record and analyze the fluorescence of DNA and its associated proteins in real time. The researchers also demonstrated that they can take DNA stripped of its proteins, label it with a fluorescent molecule that binds to methylated bases, and detect specific locations of DNA methylation.

In this set of experiments, the researchers used their nanofluidic system to reveal the frequency and coincidence of epigenetic changes in single DNA molecules. The investigators believe, however, that they will be able to modify the device to rapidly sort DNA-protein structures based on their epigenetic signatures. The sorted chromatin fragments could then be studied further using all the tools of DNA, including DNA sequencing.

his work is detailed in a paper titled, "Single Molecule Epigenetic Analysis in a Nanofluidic Channel." An abstract of this paper is available at the journal's Web site.

Explore further: Scientists clarify a mechanism of epigenetic inheritance

Related Stories

Scientists clarify a mechanism of epigenetic inheritance

April 22, 2008

Although letters representing the three billion pairs of molecules that form the “rungs” of the helical DNA “ladder” are routinely called the human “genetic code,” the DNA they comprise transmits traits across ...

Large DNA stretches, not single genes, shut off as cells mature

January 18, 2009

Experiments at Johns Hopkins have found that the gradual maturing of embryonic cells into cells as varied as brain, liver and immune system cells is apparently due to the shut off of several genes at once rather than in individual ...

USC researchers explore genetic causes for male infertility

December 12, 2007

Researchers at the University of Southern California (USC) suggest epigenetics, or the way DNA is processed and expressed, may be the underlying cause for male infertility. The study will be published in the Dec. 12 issue ...

Epigenetic signals differ across alleles

February 12, 2010

Researchers from the Institute of Psychiatry (IoP), King's College London, have identified numerous novel regions of the genome where the chemical modifications involved in controlling gene expression are influenced by either ...

Recommended for you

Particles self-assemble into Archimedean tilings

December 8, 2016

(—For the first time, researchers have simulated particles that can spontaneously self-assemble into networks that form geometrical arrangements called Archimedean tilings. The key to realizing these structures ...

Nano-calligraphy on graphene

December 8, 2016

Scientists at The University of Manchester and Karlsruhe Institute of Technology have demonstrated a method to chemically modify small regions of graphene with high precision, leading to extreme miniaturisation of chemical ...

ANU invention to inspire new night-vision specs

December 7, 2016

Scientists at The Australian National University (ANU) have designed a nano crystal around 500 times smaller than a human hair that turns darkness into visible light and can be used to create light-weight night-vision glasses.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.