Abstract
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.
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Abbreviations
- 5caC:
-
5-Carboxylcytosine
- 5fC:
-
5-Formylcytosine
- 5hmC:
-
5-Hydroxymethylcytosine
- 5mC:
-
5-Methylcytosine
- Aba-seq:
-
AbaSI-coupled sequencing
- Ccf:
-
DNA circulating cell-free DNA
- ChIP:
-
Chromatin immunoprecipitation
- CMS:
-
5-Cytosinemethylenesulfonate
- COBRA:
-
Combined bisulfite restriction analysis
- COLD:
-
Coamplification at lower denaturation temperature
- ddPCR:
-
Digital droplet PCR
- DREAM:
-
Digital restriction enzyme analysis of methylation
- FFPE:
-
Formalin fixed paraffin embedded
- GLIB:
-
Glucosylation, periodate oxidation, biotinylation
- HELP:
-
HpaII tiny fragment enrichment by ligation-mediated PCR
- HELP-GT:
-
HpaII tiny fragment enrichment by ligation-mediated PCR-glycosyl transferase assay
- hMeSEAL:
-
5hmC-selective chemical labeling
- M:
-
Million
- MALDI-TOF-MS/MALDI-MS:
-
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
- MBD:
-
Methyl-binding domain
- MSDK:
-
Methylation-specific digital karyotyping
- MeDIP:
-
Methylated DNA immunoprecipitation
- MIRA:
-
Methylated-CpG island recovery assay
- MRE:
-
Methylation-specific restriction enzyme
- MS:
-
Methylation sensitive
- MSCC:
-
Methylation-specific cut counting
- MS-FLAG:
-
Methylation-sensitive fluorescent amplicon generation
- MS-HRM:
-
Methylation-specific high-resolution melting analysis
- MS-MLPA:
-
Methylation-specific multiplexed ligation probe amplification
- MSP:
-
Methylation-specific PCR
- MS-SNuPE:
-
Methylation-specific single-nucleotide primer extension
- NGS:
-
Next-/second-generation sequencing
- OxBS:
-
Oxidative bisulfite
- PBAT:
-
Post-bisulfite adaptor tagging
- PBMC:
-
Peripheral blood mononuclear cells
- QAMA:
-
Quantitative analysis of methylated alleles
- RRBS:
-
Reduced representation bisulfite sequencing
- RRHP:
-
Reduced representation 5-hydroxymethylcytosine profiling
- SBS:
-
Sequencing by synthesis
- SCAN:
-
Single chromatin molecule analysis at the nanoscale
- SMART-MSP:
-
Sensitive melting analysis after real-time methylation-specific PCR
- SMRT:
-
Single-molecule real time
- SuBLiME:
-
Streptavidin bisulfite ligand methylation enrichment
- TAB-seq:
-
TET-assisted bisulfite sequencing
- TET:
-
Ten-eleven translocation (enzyme)
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Acknowledgments
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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Tost, J. (2016). Current and Emerging Technologies for the Analysis of the Genome-Wide and Locus-Specific DNA Methylation Patterns. In: Jeltsch, A., Jurkowska, R. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 945. Springer, Cham. https://doi.org/10.1007/978-3-319-43624-1_15
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