Single-Molecule, Genome-Scale Analyses of DNA Modifications: Exposing the Epigenome with Next-Generation Technologies

Abstract

DNA modifications represent an integral part of the epigenome and they have a pivotal role in regulation of genome function. Despite the wide variety of analytical techniques that have been developed to detect DNA modifications, their investigation at the single-genome level is only beginning to emerge. In contrast to population-averaged analyses, single-molecule approaches potentially allow the mapping of epigenetic linkage between distantly located genomic regions, the locus-specific analysis of repetitive DNA elements, as well as determination of allele-specific DNA modification patterns. In this article, the properties of current single-molecule analyses of DNA modifications will be discussed and compared. In addition, the possible biomedical and discovery research applications of single-molecule epigenomics will be highlighted.

KEYWORDS::

• 5-hydroxymethylcytosine
• 5-methylcytosine
• DNA combing
• DNA methylation
• epigenetic biomarkers
• nanopore sequencing
• repetitive DNA
• SMRT sequencing

Financial & competing interests disclosure

This work was supported by the Deutsche Forschungsgemeinschaft SFB960 grant (A Németh). K Zillner is a PhD fellow of the Bavarian Elite Network. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by the Deutsche Forschungsgemeinschaft SFB960 grant (A Németh). K Zillner is a PhD fellow of the Bavarian Elite Network. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.