Sequencing the Sixth Base (5‐Hydroxymethylcytosine): Selective DNA Oxidation Enables Base‐Pair Resolution

Abstract

Sodium bisulfite promotes both the deformylative deamination of 5-formylcytosine (5fC) and the decarboxylative deamination of 5-carboxylcytosine (5caC; see picture). By coupling this bisulfite chemistry with selective oxidations of individual DNA bases, new methods allow, for the first time, the sequencing of 5-hydroxymethylcytosine (5hmC) with single-base-pair resolution.