Current and Emerging Technologies for the Analysis of the Genome-Wide and Locus-Specific DNA Methylation Patterns

  • Jörg TostEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 945)


DNA methylation is the most studied epigenetic modification, and altered DNA methylation patterns have been identified in cancer and more recently also in many other complex diseases. Furthermore, DNA methylation is influenced by a variety of environmental factors, and the analysis of DNA methylation patterns might allow deciphering previous exposure. Although a large number of techniques to study DNA methylation either genome-wide or at specific loci have been devised, they all are based on a limited number of principles for differentiating the methylation state, viz., methylation-specific/methylation-dependent restriction enzymes, antibodies or methyl-binding proteins, chemical-based enrichment, or bisulfite conversion. Second-generation sequencing has largely replaced microarrays as readout platform and is also becoming more popular for locus-specific DNA methylation analysis. In this chapter, the currently used methods for both genome-wide and locus-specific analysis of 5-methylcytosine and as its oxidative derivatives, such as 5-hydroxymethylcytosine, are reviewed in detail, and the advantages and limitations of each approach are discussed. Furthermore, emerging technologies avoiding PCR amplification and allowing a direct readout of DNA methylation are summarized, together with novel applications, such as the detection of DNA methylation in single cells or in circulating cell-free DNA.


Bisulfite Sequencing Bisulfite Conversion Bisulfite Treatment Methylation Variable Position Amplicon Bisulfite Sequencing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.











AbaSI-coupled sequencing


DNA circulating cell-free DNA


Chromatin immunoprecipitation




Combined bisulfite restriction analysis


Coamplification at lower denaturation temperature


Digital droplet PCR


Digital restriction enzyme analysis of methylation


Formalin fixed paraffin embedded


Glucosylation, periodate oxidation, biotinylation


HpaII tiny fragment enrichment by ligation-mediated PCR


HpaII tiny fragment enrichment by ligation-mediated PCR-glycosyl transferase assay


5hmC-selective chemical labeling




Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry


Methyl-binding domain


Methylation-specific digital karyotyping


Methylated DNA immunoprecipitation


Methylated-CpG island recovery assay


Methylation-specific restriction enzyme


Methylation sensitive


Methylation-specific cut counting


Methylation-sensitive fluorescent amplicon generation


Methylation-specific high-resolution melting analysis


Methylation-specific multiplexed ligation probe amplification


Methylation-specific PCR


Methylation-specific single-nucleotide primer extension


Next-/second-generation sequencing


Oxidative bisulfite


Post-bisulfite adaptor tagging


Peripheral blood mononuclear cells


Quantitative analysis of methylated alleles


Reduced representation bisulfite sequencing


Reduced representation 5-hydroxymethylcytosine profiling


Sequencing by synthesis


Single chromatin molecule analysis at the nanoscale


Sensitive melting analysis after real-time methylation-specific PCR


Single-molecule real time


Streptavidin bisulfite ligand methylation enrichment


TET-assisted bisulfite sequencing


Ten-eleven translocation (enzyme)



Work in the laboratory of Jörg Tost is supported by grants from the ANR (ANR-13-EPIG-0003-05 and ANR-13-CESA-0011-05), Aviesan/INSERM (EPIG2014-01 and EPlG2014-18), INCa (PRT-K14-049), the joint CEA-EDF-IRSN program (CP-PHE-102), a Sirius Research Award (UCB Pharma S.A.), and the institutional budget of the CNG.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Laboratory for Epigenetics and EnvironmentCentre National de Génotypage, CEA-Institut de GénomiqueEvryFrance

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