Toward single-molecule optical mapping of the epigenome

Michal Levy-Sakin, Assaf Grunwald, Soohong Kim, Natalie R. Gassman, Anna Gottfried, Josh Antelman, Younggyu Kim, Sam O. Ho, Robin Samuel, Xavier Michalet, Ron R. Lin, Thomas Dertinger, Andrew S. Kim, Sangyoon Chung, Ryan A. Colyer, Elmar Weinhold, Shimon Weiss*, Yuval Ebenstein

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


The past decade has seen an explosive growth in the utilization of single-molecule techniques for the study of complex systems. The ability to resolve phenomena otherwise masked by ensemble averaging has made these approaches especially attractive for the study of biological systems, where stochastic events lead to inherent inhomogeneity at the population level. The complex composition of the genome has made it an ideal system to study at the single-molecule level, and methods aimed at resolving genetic information from long, individual, genomic DNA molecules have been in use for the last 30 years. These methods, and particularly optical-based mapping of DNA, have been instrumental in highlighting genomic variation and contributed significantly to the assembly of many genomes including the human genome. Nanotechnology and nanoscopy have been a strong driving force for advancing genomic mapping approaches, allowing both better manipulation of DNA on the nanoscale and enhanced optical resolving power for analysis of genomic information. During the past few years, these developments have been adopted also for epigenetic studies. The common principle for these studies is the use of advanced optical microscopy for the detection of fluorescently labeled epigenetic marks on long, extended DNA molecules. Here we will discuss recent single-molecule studies for the mapping of chromatin composition and epigenetic DNA modifications, such as DNA methylation.

Original languageEnglish
Pages (from-to)14-26
Number of pages13
JournalACS Nano
Issue number1
StatePublished - 28 Jan 2014


  • chromatin
  • epigenetics
  • fluorescence microscopy
  • methylation
  • nanoscopy
  • nanotechnology
  • optical mapping
  • single molecule


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