Epigenomic profiling of active regulatory elements by enrichment of unmodified CpG dinucleotides

In this study we present an enrichment-based and bisulfite-free approach for epigenomic profiling named 'Active-Seq' (Azide Click Tagging for In Vitro Epigenomic sequencing) that achieves genome-wide profiling of DNA, by enriching for non-modified CpG sites using a mutated methyltransferase enzyme. Active-Seq is a fast epigenetic profiling platform with a simple and streamlined workflow, performed in tandem with sequencing library preparation. The enzymatic chemistry is non-damaging toward the DNA which is critical for working with low concentration DNA input and will facilitate the future development of multiomics assays. Overall design: In order to compare Active-seq to orthogonal technologies, we performed Active-seq and MeDIP-seq on DNA derived from GM12878 cell line and compared the processed signal. In order to measure the reproducibility of the Active-Seq assay, we performed Active-Seq in three replicates in the following cell lines: MCF7, HEPG2, SW48, HT29, HCC1937.