Endonuclease enrichment TAPS for cost-effective genome-wide base-resolution DNA methylation detection. Issue 13 (27th April 2021)

• Record Type: Journal Article
• Authors: Cheng, Jingfei; Siejka-Zielińska, Paulina; Liu, Yibin; Chandran, Anandhakumar; Kriaucionis, Skirmantas; Song, Chun-Xiao
• Is Part Of: Nucleic acids research. Volume 49:Issue 13(2021)
• Page Start: e76
• Page End: e76
• Publication Date: 2021-04-27
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkab291
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Whole genome base-resolution methylome sequencing allows for the most comprehensive analysis of DNA methylation, however, the considerable sequencing cost often limits its applications. While reduced representation sequencing can be an affordable alternative, over 80% of CpGs in the genome are not covered. Building on our recently developed TET-assisted pyridine borane sequencing (TAPS) method, we here described endonuclease enrichment TAPS (eeTAPS), which utilizes dihydrouracil (DHU)-cleaving endonuclease digestion of TAPS-converted DNA to enrich methylated CpG sites (mCpGs). eeTAPS can accurately detect 87% of mCpGs in the mouse genome with a sequencing depth equivalent to 4× whole genome sequencing. In comparison, reduced representation TAPS (rrTAPS) detected less than 4% of mCpGs with 2.5× 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.