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.

绘制与染色质上 DNA 或蛋白质结合的小分子药物的图谱对于了解其功能至关重要。研究表观遗传景观中的这些结合动态可以提高我们对细胞类型特异性药物作用的理解。 Dong 等人在《自然方法》上发表的一篇论文。推出了 scEpiChem，这是一种将小分子药物结合与单细胞多模式表观遗传分析相结合的方法。

scEpiChem 使用抗生物素抗体捕获的生物素化小分子药物，然后使用条形码蛋白 A-Tn5 和组合条形码进行靶向标记。作者用三种小分子药物验证了这种方法：BET 溴结构域蛋白抑制剂 JQ1、CDK7 抑制剂 THZ1 和拓扑异构酶 II 抑制剂阿霉素。然后，他们整合了目标蛋白分析和表观基因组特征，例如组蛋白修饰和染色质可及性。