Bisulfite Methylation Profiling of Large Genomes

Abstract

Bisulfite conversion of genomic DNA differentiates cytosines from 5-methylcytosines and, thus, identifies DNA methylation patterns at the single-base level. Here, we review recent developments incorporating high-throughput sequencing of bisulfite-converted DNA for target-specific analyses and genome-wide mapping of plant and mammalian methylomes. These developments include the analysis of human embryonic stem cell and fetal fibroblast methylomes at single-base resolution, which supports the presence of non-CG DNA methylation in wild-type embryonic stem cells and induced pluripotent stem cells. New developments in nanopore sequencing technologies may lead to directly detecting 5-methylcytosine independently of bisulfite conversion, but the current accuracy of this approach remains a limitation. Furthermore, recent investigations detecting 5-hydroxymethylcytosine within mammalian DNA may add yet another level of complexity to the epigenetic code of the methylome.

KEYWORDS::

• 5-methylcytosine
• bisulfite
• DNA methylation
• high-throughput sequencing
• methylome

Acknowledgements

The authors would like to thank Dr Patrick King for reviewing this manuscript.

Financial & competing interests disclosure

This work was supported by grants from the Swiss National Science Foundation (3100A0–102107) and the European Commission through The Epigenome (LSHG-CT-2004–503433). 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 grants from the Swiss National Science Foundation (3100A0–102107) and the European Commission through The Epigenome (LSHG-CT-2004–503433). 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.