A substantial number of small-molecule ligands, including therapeutic drugs, elicit their effects by binding specific proteins associated with the genome. Mapping the global interactions of these chemical entities with chromatin in a genome-wide manner could provide insights into the mechanisms by which a small molecule influences cellular functions. When combined with other chromatin analysis techniques such as ChIP-seq,[2] Chem-seq can be utilized to investigate the genome-wide effects of therapeutic modalities and to understand the effects of drugs on nuclear architecture in various biological contexts.