Genome-wide determination of drug localization

• Published in: Nature biotechnology Vol. 32; no. 1; pp. 92 - 96
• Main Authors: Anders, Lars, Guenther, Matthew G., Qi, Jun, Fan, Zi Peng, Marineau, Jason J., Rahl, Peter B., Lovén, Jakob, Sigova, Alla A., Smith, William B., Lee, Tong Ihn, Bradner, James E., Young, Richard A.
• Format: Journal Article
• Language: English
• Published: 15-12-2013
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.2776

A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide new and important insights into chemical perturbation of cellular function. Here we describe a method that couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq) to identify the sites bound by small chemical molecules throughout the human genome. We show how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. These methods provide a powerful approach to enhance understanding of therapeutic action and characterize the specificity of chemical entities that interact with DNA or genome-associated proteins.