Genome-wide localization of small molecules

• Main Authors: Anders, Lars (Author), Guenther, Matthew G. (Author), Qi, Jun (Author), Fan, Zi Peng (Contributor), Marineau, Jason J (Author), Rahl, Peter B (Author), Sigova, Alla A (Author), Smith, William B (Author), Lee, Tong Ihn (Author), Bradner, James E. (Author), Young, Richard A. (Contributor), Loven, Jakob (Author)
• Other Authors: Massachusetts Institute of Technology. Computational and Systems Biology Program (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Whitehead Institute for Biomedical Research (Contributor)
• Format: Article
• Language: English
• Published: Nature Publishing Group, 2015-04-30T12:42:34Z.
• Subjects: Article
• Online Access: Get fulltext

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 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 will be broadly useful to enhance understanding of therapeutic action and to characterize the specificity of chemical entities that interact with DNA or genome-associated proteins.
National Institutes of Health (U.S.) (Grant HG002668)
National Institutes of Health (U.S.) (Grant CA109901)
National Institutes of Health (U.S.) (Grant CA146445)