DNA Readers: Cracking the Epigenetic Code Using Nanoscale Electrodes

Very exciting developments on the detection of DNA markers has recently been published by scientists at Osaka University. Nanowerk News (http://www.nanowerk.com) has provided an overview of their research, which is provided below. The publication reference, abstract and link to where you can obtain the full publication is also provided.

Overview from Nanowerk News

Decoding some of the subtler information encoded in our DNA could soon become a high-throughput process, a team of researchers in Japan have shown. Masateru Taniguchi and colleagues at Osaka University have shown that DNA-borne chemical markers, which play a key role in gene expression, can be detected electrically using nanoscale electrodes (as DNA is passed through a nanoscale gap between two electrodes, a measurable current is generated allowing the detection of DNA markers).

The team's technology is a step toward understanding the meaning of some of the molecular modifiers that nature uses to annotate DNA strands. These modifiers, also known as epigenetic markers, alter over time and are thought to play a key role in processes ranging from embryo development to aging and disease. But just how the markers work, and what different markers mean, remains to be unraveled.

Deciphering the epigenetic code is a massive mapping exercise, but will provide important information on how epigenetic markers differ among cell types and between healthy and sick individuals. Actually detecting the markers, however, has proved difficult. One of the most common markers is an individual methyl group, which consists of a single carbon atom and three hydrogen atoms, and its detection has previously required the attachment of additional chemical labels. "But such an approach is troublesome and takes a lot of time," says Taniguchi. The ability to detect markers such as methyl groups directly would therefore open up immense opportunities for epigenetic research.

Taniguchi and his colleagues explored the possibility of direct marker detection by analyzing a small strip of DNA as it passes between two electrodes positioned just a nanometer apart (see image). An electrical current flows as the DNA squeezes between the electrodes, and the size of the current depends on the chemical make-up of the DNA within the gap. This allows any molecular marker on the DNA, including individual methyl groups, to be detected electrically.

The key issue for turning the technology into a practical, rapid DNA-reading device is achieving precise control of the movement of the DNA strand through the electrode nanopore. "Recently, we have theoretically proposed a way to control DNA strand flow using a gate," Taniguchi explains. "We are now developing a gating nanopore device as a proof-of-principle demonstration of this electrical gating scheme."

Reference

Electrical Detection of Single Methylcytosines in a DNA Oligomer.

Makusu Tsutsui†, Kazuki Matsubara†, Takahito Ohshiro†, Masayuki Furuhashi†, Masateru Taniguchi*†, and Tomoji Kawai*†‡

† The Institute of Scientific and Industrial Research,Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.

‡ Division of Quantum Phases and Devices, Department of Physics, Konkuk University, Seoul 143-701, Republic of Korea.

J. Am. Chem. Soc., 2011, 133 (23), pp 9124–9128.

Abstract

We report label-free electrical detections of chemically modified nucleobases in a DNA using a nucleotide-sized electrode gap. We found that methyl substitution contributes to increase the tunneling conductance of deoxycytidines, which was attributed to a shift of the highest occupied molecular orbital level closer to the electrode Fermi level by methylation. We also demonstrate statistical identifications of methylcytosines in an oligonucleotide by tunneling current. This result suggests a possible use of the transverse electron-transport method for a methylation level analysis.