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Whole Genome DNA Methylation: Beyond Genes Silencing. (Oncotarget, Nov 2016)

Tirado-Magallanes R1,2, Rebbani K1, Lim R1, Pradhan S3, Benoukraf T1

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.

Abstract

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.

KEYWORDS: DNA methylation; bisulfite sequencing; chromatin modeling; gene regulation; imprinting

PMID: 27895318