Genome-wide localization of small molecules
Author(s)Anders, Lars; Guenther, Matthew G.; Qi, Jun; Fan, Zi Peng; Marineau, Jason J; Rahl, Peter B; Sigova, Alla A; Smith, William B; Lee, Tong Ihn; Bradner, James E.; Young, Richard A.; Loven, Jakob; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Computational and Systems Biology Program; Massachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Nature Publishing Group
Anders, Lars, Matthew G Guenther, Jun Qi, Zi Peng Fan, Jason J Marineau, Peter B Rahl, Jakob Loven, et al. “Genome-Wide Localization of Small Molecules.” Nature Biotechnology 32, no. 1 (December 15, 2013): 92–96.
Author's final manuscript