Nanomechanical recognition measurements of individual DNA molecules reveal epigenetic methylation patterns.

Abstract

Atomic force microscopy (AFM) is a powerful tool for analysing the shapes of individual molecules and the forces acting on them. AFM-based force spectroscopy provides insights into the structural and energetic dynamics of biomolecules by probing the interactions within individual molecules, or between a surface-bound molecule and a cantilever that carries a complementary binding partner. Here, we show that an AFM cantilever with an antibody tether can measure the distances between 5-methylcytidine bases in individual DNA strands with a resolution of 4 Å, thereby revealing the DNA methylation pattern, which has an important role in the epigenetic control of gene expression. The antibody is able to bind two 5-methylcytidine bases of a surface-immobilized DNA strand, and retracting the cantilever results in a unique rupture signature reflecting the spacing between two tagged bases. This nanomechanical approach might also allow related chemical patterns to be retrieved from biopolymers at the single-molecule level.

• Authors: Rong Zhu, Stefan Howorka, Johannes Pröll, Ferry Kienberger, Johannes Preiner, Jan Hesse, Andreas Ebner, Vassili Ph Pastushenko, Hermann J Gruber, Peter Hinterdorfer
• Journal: Nature nanotechnology (Nat Nanotechnol) Vol. 5 Issue 11 Pg. 788-91 (Nov 2010) ISSN: 1748-3395 [Electronic] England
• PMID: 21037576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Single-Stranded
• Cytidine
• 5-methylcytidine

Topics

• Cytidine (analogs & derivatives, chemistry)
• DNA Methylation
• DNA, Single-Stranded (chemistry)
• Epigenesis, Genetic
• Microscopy, Atomic Force
• Nanotechnology (methods)
• Nucleic Acid Conformation