Advances in the Profiling of Single‐Cell DNA Modifications

Abstract Epigenetic modifications on DNA include canonical 5‐methylcytosine (5mC) and its iteratively oxidized derivatives mediated by TET dioxygenase: 5‐hydroxymethylcytosine (5hmC), 5‐formylcytosine (5fC), and 5‐carboxycytosine (5caC). All of them have been recognized to play important roles in gene expression regulation and to be indispensable for normal mammalian reproduction and development. In order to understand the mechanisms underlying these roles, over the past few decades, technical advances have been made to comprehensively profile the distribution pattern of bulk epigenetic modifications in genomic DNA. Recently, single‐cell methods have identified the epigenetic patterns even within an individual cell. This review focuses on single‐cell DNA epigenetic modifications sequencing technologies and their applications, and gives prospects on the development of single‐cell methods based on bisulfite‐free strategy.