Endonuclease enrichment TAPS for cost-effective genome-wide base-resolution DNA methylation detection

We described endonuclease enrichment TAPS (eeTAPS), which utilizes dihydrouracil (DHU)-sensitive endonuclease digestion after TAPS to enrich methylated CpG (mCpG). eeTAPS can accurately detect 87% of methylated CpGs in the mouse genome with a sequencing depth comparable to 4x whole genome sequencing. In comparison, reduced representation TAPS (rrTAPS) detected less than 4% of methylated CpGs with 2.5x sequencing depth. Our results demonstrate eeTAPS to be a new strategy for cost-effective genome-wide methylation analysis at single-CpG resolution that can fill the gap between whole-genome and reduced representation sequencing. Overall design: 5-Methylcytosine and 5-hydroxymethylcytosine detection with eeTAPS and rrTAPS in E14 mESC cell line.