Hu Qiu, Aditya Sarathy, Klaus Schulten, and Jean-Pierre Leburton.
Detection and mapping of DNA methylation with 2D material
nanopores.
npj 2D Materials and Applications, 1:3, 2017.
(PMC: PMC5794036)
QIU2017
DNA methylation is an epigenetic modification involving the addition of a methyl
group to DNA, which is heavily involved in gene expression and regulation, thereby
critical to the progression of diseases such as cancer. In this work we show that detection and localization of DNA methylation can be achieved with nanopore sensors
made of two-dimensional (2D) materials such as graphene and molybdenum di-sulphide
(MoS2). We label each DNA methylation site with a methyl-CpG binding domain protein (MBD1), and combine molecular dynamics simulations with electronic transport
calculations to investigate the translocation of the methylated DNA-MBD1 complex
through 2D material nanopores under external voltage biases. The passage of the
MBD1-labeled methylation site through the pore is identified by dips in the current blockade induced by the DNA strand, as well as by peaks in the transverse electronic
sheet current across the 2D layer. The position of the methylation sites can be clearly
recognized by the relative positions of the dips in the recorded ionic current blockade with an estimated error ranging from 0% to 16%. Finally, we define the spatial
resolution of the 2D material nanopore device as the minimal distance between two
methylation sites identified within a single measurement, which is 15 base pairs by ionic
current recognition, but as low as 10 base pairs by transverse electronic conductance
detection, indicating better resolution with this latter technique. The present approach
opens a new route for precise and efficient profiling of DNA methylation.
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