Mapping small-molecule drugs that bind DNA or protein on chromatin is fundamental for understanding their function. Studying these binding dynamics within the epigenetic landscape could improve our understanding of cell-type-specific drug actions. A paper in Nature Methods by Dong et al. introduces scEpiChem, a method that combines small-molecule drug binding with multimodal epigenetic profiling in single cells.

scEpiChem uses biotinylated small-molecule drugs captured with an anti-biotin antibody, followed by targeted tagmentation using barcoded protein A-Tn5 and combinatorial barcoding. The authors validated this approach with three small-molecule drugs: the BET bromodomain protein inhibitor JQ1, the CDK7 inhibitor THZ1 and the topoisomerase II inhibitor doxorubicin. They then incorporated target protein profiling and epigenomic features, such as histone modifications and chromatin accessibility.