Whole genome DNA methylation: beyond genes silencing

Roberto Tirado-Magallanes _, Khadija Rebbani, Ricky Lim, Sriharsa Pradhan and Touati Benoukraf

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Oncotarget. 2017; 8:5629-5637. https://doi.org/10.18632/oncotarget.13562

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Roberto Tirado-Magallanes1,2, Khadija Rebbani1, Ricky Lim1, Sriharsa Pradhan3, Touati Benoukraf1

1Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore, Singapore

2Computational Systems Biology Team, Institut de Biologie de l’Ecole Normale Supérieure (IBENS), INSERM, Ecole Normale Supérieure, PSL Research University, 75005 Paris, France

3New England Biolab Inc., Ipswich, MA 01938, USA

Correspondence to:

Touati Benoukraf, email: [email protected]

Keywords: DNA methylation, bisulfite sequencing, gene regulation, chromatin modeling, imprinting

Received: August 11, 2016     Accepted: November 07, 2016     Published: November 24, 2016


The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation at near base pair level resolution, far beyond that of the kilobase-long canonical CpG islands that initially revealed the biological relevance of this covalent DNA modification. The latest high-resolution studies have revealed a role for very punctual DNA methylation in chromatin plasticity, gene regulation and splicing. Here, we aim to outline the major biological consequences of DNA methylation recently discovered. We also discuss the necessity of tuning DNA methylation resolution into an adequate scale to ease the integration of the methylome information with other chromatin features and transcription events such as gene expression, nucleosome positioning, transcription factors binding dynamic, gene splicing and genomic imprinting. Finally, our review sheds light on DNA methylation heterogeneity in cell population and the different approaches used for its assessment, including the contribution of single cell DNA analysis technology.

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