title: Unravelling the genomic targets of small molecules using high-throughput sequencing.
abstract: Small molecules--including various approved and novel cancer therapeutics--can operate at the genomic level by targeting the DNA and protein components of chromatin. Emerging evidence suggests that functional interactions between small molecules and the genome are non-stochastic and are influenced by a dynamic interplay between DNA sequences and chromatin states. The establishment of genome-wide maps of small-molecule targets using unbiased methodologies can help to characterize and exploit drug responses. In this Review, we discuss how high-throughput sequencing strategies, such as ChIP-seq (chromatin immunoprecipitation followed by sequencing) and Chem-seq (chemical affinity capture and massively parallel DNA sequencing), are enabling the comprehensive identification of small-molecule target sites throughout the genome, thereby providing insights into unanticipated drug effects.
authors.affiliation: 1] Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles du CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France. [2] Institut Curie Research Center, Organic Synthesis and Cell Biology Group, 26 rue d'Ulm, 75248, Paris Cedex 05, France. [3].
authors.forename: Raphaël
authors.initials: R
authors.lastname: Rodriguez
authors.affiliation: 1] Department of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, 2506 Speedway Stop A5000, Austin, Texas 78712, USA. [2].
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Miller
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D016503:Drug Delivery Systems; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017422:Sequence Analysis, DNA; D054852:Small Molecule Libraries
chemical_list: D054852:Small Molecule Libraries