title: Genome-Wide Assessment of the Binding Effects of Artificial Transcriptional Activators by High-Throughput Sequencing.
abstract: One of the major goals in DNA-based personalized medicine is the development of sequence-specific small molecules to target the genome. SAHA-PIPs belong to such class of small molecule. In the context of the complex eukaryotic genome, the differential biological effects of SAHA-PIPs are unclear. This question can be addressed by identifying the binding regions across the genome; however, it is a challenge to enrich small-molecule-bound DNA without chemical crosslinking. Here, we developed a method that employs high-throughput sequencing to map the binding area of small molecules throughout the chromatinized human genome. Analysis of the sequenced data confirmed the presence of specific binding sites for SAHA-PIPs from the enriched sequence reads. Mapping the binding sites and enriched regions on the human genome clarifies the reason for the distinct biological effects of SAHA-PIP. This approach will be useful for identifying the function of other small molecules on a large scale.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Anandhakumar
authors.initials: A
authors.lastname: Chandran
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Junetha
authors.initials: J
authors.lastname: Syed
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto, 606-8501, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan. hs@kuchem.kyoto-u.ac.jp.|Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto, 606-8501, Japan. hs@kuchem.kyoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015394:Molecular Structure; D009757:Nylons / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000077337:Vorinostat
chemical_list: D006877:Hydroxamic Acids; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D000077337:Vorinostat; D004247:DNA; C096654:N-methylpyrrole; C018100:1-methylimidazole
keywords: SAHA-PIP; epigenetics; genomics; high-throughput screening; pull-down; small molecule