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

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

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.

Keywords

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.

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)

Notes

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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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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