Oct 16, 2016

Whole-genome analysis of the methylome and hydroxymethylome in normal and malignant lung and liver

Genome Research
Xin LiAndrew P Feinberg

Abstract

DNA methylation at the 5-position of cytosine (5mC) is an epigenetic modification that regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), providing an active mechanism for DNA demethylation, and it may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in human normal liver and lung as well as paired tumor tissues. We found that 5hmC is significantly enriched in CpG island (CGI) shores while depleted in CGIs themselves, especially in active genes, which exhibit a bimodal distribution of 5hmC around CGI that corresponds to H3K4me1 modifications. Hydroxymethylation on promoters, gene bodies, and transcription termination regions (TTRs) showed strong positive correlation with gene expression within and across tissues, suggesting that 5hmC is a marker of active genes and could play a role in gene expression mediated by DNA demethylation. Comparative analysis of methylomes and hydroxymethylomes revealed that 5hmC is significantly enriched in both tissue-specific DMRs (t-DMRs) and ca...Continue Reading

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  • Citations32

References

Mentioned in this Paper

Biological Markers
Genome-Wide Association Study
Study
Hydrogen sulfite
Positioning Attribute
DNA Methylation [PE]
Body Structure
Protein Methylation
Lung
Genome

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